Michael A. Sloan

2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.

Elliott M. Antman, MD, FACC, FAHA, Co-Chair*†; Mary Hand, MSPH, RN, FAHA, Co-Chair; Paul W. Armstrong, MD, FACC, FAHA‡§; Eric R. Bates, MD, FACC, FAHA; Lee A. Green, MD, MPH ; Lakshmi K. Halasyamani, MD¶; Judith S. Hochman, MD, FACC, FAHA**; Harlan M. Krumholz, MD, FACC, FAHA††; Gervasio A. Lamas, MD, FACC**; Charles J. Mullany, MB, MS, FACC; David L. Pearle, MD, FACC, FAHA; Michael A. Sloan, MD, FACC; Sidney C. Smith, Jr, MD, FACC, FAHA§§

2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction

Elliott M. Antman, MD, FACC, FAHA, Chair Daniel T. Anbe, MD, FACC, FAHA Paul W. Armstrong, MD, FACC, FAHA Eric R. Bates, MD, FACC, FAHA Lee A. Green, MD, MPH Mary Hand, MSPH, RN, FAHA Judith S. Hochman, MD, FACC, FAHA Harlan M. Krumholz, MD, FACC, FAHA Frederick G. Kushner, MD, FACC, FAHA

PREGNANCY AND THE RISK OF STROKE

BACKGROUND It is widely believed that pregnancy increases the risk of stroke, but there are few data available to quantify that risk. METHODS We identified all female patients 15 through 44 years of age in central Maryland and Washington, D.C., who were discharged from any of 46 hospitals in the study area in 1988 or 1991. Two neurologists reviewed each case, using data from the womens medical records. We determined whether the women had been pregnant at the time of the stroke or up to six weeks before it occurred. For purposes of this analysis, the six-week period after pregnancy could begin with an induced or spontaneous abortion or with the delivery of a live or stillborn child. RESULTS Seventeen cerebral infarctions and 14 intracerebral hemorrhages occurred in women who were or had recently been pregnant (pregnancy-related strokes), and there were 175 cerebral infarctions and 48 intracerebral hemorrhages that were not related to pregnancy. For cerebral infarction, the relative risk during pregnancy, adjusted age and race, was 0.7 (95 percent confidence interval, 0.3 to 1.6), but it increased to 8.7 for the postpartum period (after a live birth or stillbirth) (95 percent confidence interval, 4.6 to 16.7). For intracerebral hemorrhage, the adjusted relative risk was 2.5 during pregnancy (95 percent confidence interval, 1.0 to 6.4) but 28.3 for the postpartum period (95 percent confidence interval, 13.0 to 61.4). Overall, for either type of stroke during or within six weeks after pregnancy, the adjusted relative risk was 2.4 (95 percent confidence interval, 1.6 to 3.6), and the attributable, or excess, risk was 8.1 strokes per 100,000 pregnancies (95 percent confidence interval, 6.4 to 9.7). CONCLUSIONS The risks of both cerebral infarction and intracerebral hemorrhage are increased in the six weeks after delivery but not during pregnancy itself.

Assessment: Transcranial Doppler ultrasonography: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

Objective: To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. Methods: The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. Results: TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.Objective:To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. Methods:The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. Results:TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.

Stroke After Thrombolysis Mortality and Functional Outcomes in the GUSTO-I Trial

BACKGROUND Stroke is the most feared complication of thrombolysis for acute myocardial infarction because of the resulting mortality and disability. We analyzed the incidence, timing, and outcomes of stroke in an international trial. METHODS AND RESULTS Patients were randomly assigned to one of four thrombolytic strategies. Neurological events were confirmed clinically and anatomically and were adjudicated by a blinded committee. Stroke survivors, categorized by residual deficit and disability, assessed their quality of life with a time trade-off technique. Multivariable regression identified patient characteristics associated with intracranial hemorrhage. Over-all, 1.4% of the patients had a stroke (93% anatomic documentation). The risk ranged from 1.19% with streptokinase/subcutaneous heparin therapy to 1.64% with combination thrombolytic therapy (P = .007). Primary intracranial hemorrhage rates ranged from 0.46% with streptokinase/subcutaneous heparin to 0.88% with combination therapy (P < .001). Of all strokes, 41% were fatal, 31% were disabling, and 24% were nondisabling, with no significant treatment-related differences. Stroke subtype affected prognosis: 60% of patients with primary intracranial hemorrhage died and 25% were disabled versus 17% dead and 40% disabled with nonhemorrhagic infarctions. Patients with moderate or severe residual deficits showed significantly decreased quality of life. Advanced age, lower weight, prior cerebrovascular disease or hypertension, systolic and diastolic blood pressures, randomization to tissue plasminogen activator, and an interaction between age and hypertension were significant predictors of intracranial hemorrhage. CONCLUSIONS Stroke remains a rare but catastrophic complication of thrombolysis. Additional studies should assess the net clinical benefit of thrombolysis in high-risk subgroups, particularly the elderly and patients with prior cerebrovascular events.

Intracerebral hemorrhage, cerebral infarction, and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the Thrombolysis in Myocardial Infarction Study. Thrombolysis in Myocardial Infarction, Phase II, pilot and clinical trial.

In the Thrombolysis in Myocardial Infarction, Phase II pilot and clinical trial, 908 patients [326 (35.9%) in the pilot study and 582 (64.0%) in the randomized study] were treated with 150 mg recombinant tissue-type plasminogen (rt-PA) activator in combination with heparin and aspirin, and 3,016 patients [64 (2.1%) in the pilot study and 2,952 (97.9%) in the randomized study] were treated with 100 mg rt-PA in combination with heparin and aspirin. Adverse neurological events occurred in 23 patients treated with 150 mg rt-PA (2.5%) [nine cerebral infarctions (1.0%), 12 intracerebral hemorrhages (1.3%), and two subdural hematomas (0.2%)] and in 33 patients treated with 100 mg rt-PA (1.1%) [20 cerebral infarctions (0.7%), 11 intracerebral hemorrhages (0.4%), and two subdural hematomas (0.1%)]. The difference in adverse neurological events observed comparing the two rt-PA regimens was primarily due to a higher frequency of intracerebral bleeding among patients treated with 150 mg rt-PA (1.3% versus 0.4%, p less than 0.01). Patients with recent (within 6 months) histories of stroke were not eligible for the study, and patients with any history of cerebrovascular disease were declared ineligible early in the study. The small number of patients (89, or 2.3%) with any history of neurological disease, intermittent cerebral ischemic attacks, or stroke who were enrolled before the stricter eligibility criteria were imposed or on the basis of incomplete baseline information experienced an increased frequency of intracerebral hemorrhage compared with patients without such histories (3.4% versus 0.5%). Mortality at 6 weeks after presentation among 23 patients who had intracerebral hemorrhage was 47.8%. Intracerebral hemorrhage is a severe but infrequent complication of rt-PA therapy for acute myocardial infarction. The combined frequency of intracerebral hemorrhage, subdural hematoma, and cerebral infarction after treatment with 100 mg rt-PA is comparable to that observed in other trials with thrombolytic agents in acute myocardial infarction.

Cerebral infarction in young adults The Baltimore-Washington Cooperative Young Stroke Study

Background: Few reports on stroke in young adults have included cases from all community and referral hospitals in a defined geographic region. Methods: At 46 hospitals in Baltimore City, 5 central Maryland counties, and Washington, DC, the chart of every patient 15 to 44 years of age with a primary or secondary diagnosis of possible cerebral arterial infarction during 1988 and 1991 was abstracted. Probable and possible etiologies were assigned following written guidelines. Results: Of 428 first strokes, 212 (49.5%) were assigned at least one probable cause, 80 (18.7%) had no probable cause but at least one possible cause, and 136 (31.8%) had no identified probable or possible cause. Of the 212 with at least one probable cause, the distribution of etiologies was cardiac embolism(31.1%), hematologic and other (19.8%), small vessel (lacunar) disease(19.8%), nonatherosclerotic vasculopathy (11.3%), illicit drug use (9.4%), oral contraceptive use (5.2%), large artery atherosclerotic disease (3.8%), and migraine (1.4%). There were an additional 69 recurrent stroke patients. Conclusions: In this hospital-based registry within a region characterized by racial/ethnic diversity, cardiac embolism, hematologic and other causes, and lacunar stroke were the most common etiologies of cerebral infarction in young adults. Nearly a third of both first and recurrent strokes had no identified cause.

Risk for intracranial hemorrhage after tissue plasminogen activator treatment for acute myocardial infarction. Participants in the National Registry of Myocardial Infarction 2

Numerous large clinical trials of thrombolytic therapy have shown impressive reductions in mortality associated with the use of thrombolytic agents in the setting of acute myocardial infarction. They have also consistently shown that thrombolysis imposes an excess risk for intracranial hemorrhage [1]. Although the incidence of intracranial hemorrhage associated with thrombolytic therapy is low, this complication is characterized by high fatality rates and substantial disability among survivors. In the Global Utilization of Streptokinase and Tissue Plasminogen Activator (tPA) for Occluded Coronary Arteries (GUSTO-I) trial, intracranial hemorrhage rates were 0.46%, 0.57%, 0.70%, and 0.88% among patients treated with streptokinase plus subcutaneous heparin, streptokinase plus intravenous heparin, accelerated tPA, and combination therapy, respectively. Sixty percent of patients who had intracranial hemorrhage died, and another 25% were disabled [2]. The underuse of thrombolysis in special patient populations, such as elderly persons, is usually attributed to concerns about the risk for bleeding, particularly intracranial hemorrhage [3, 4]. These concerns often dominate decisions about the use of thrombolytic agents in eligible elderly patients with acute myocardial infarction despite the potential for substantial survival benefits from treatment [1]. In the GUSTO-I trial [5], 0.42% of patients younger than 75 years of age treated with streptokinase and 0.52% of those treated with accelerated tPA experienced a hemorrhagic stroke by 30 days of follow-up. Among patients older than 75 years of age, these values were 1.23% and 2.08%, respectively. Simoons and colleagues [6] combined information from a national registry of thrombolytic therapy with data from multiple thrombolytic trials to identify 150 patients who had had intracranial hemorrhage and compared them with 294 patients with acute myocardial infarction who received thrombolytic therapy but did not experience this outcome. After adjustment for other factors, including type of thrombolytic agent, body weight, and presence of hypertension on admission, patients older than 65 years of age were significantly more likely to experience intracranial hemorrhage (odds ratio, 2.2 [95% CI, 1.4 to 3.5]). Most information on the risk for intracranial hemorrhage associated with thrombolytic therapy in acute myocardial infarction derives from the experience of patients participating in clinical trials, in which stringent enrollment criteria are applied before thrombolytic therapy is administered [2, 7, 8]. The experience in the community setting has not been well described. The extent to which the clinician can extrapolate clinical trial data on the benefits and the risks of therapeutic interventions to the general practice setting is often unclear [9]. We used data from an ongoing national registry of patients who were hospitalized for acute myocardial infarction to determine the frequency of and risk factors for intracranial hemorrhage in patients treated with tPA, with particular focus on the relation between advancing age and this complication. Methods Data Sources The National Registry of Myocardial Infarction 2 (NRMI 2) was initiated in June 1994 as an ongoing registry of patients who received therapy for acute myocardial infarction at selected U.S. hospitals. The registry is supported by Genentech, Inc. (South San Francisco, California). From 1 June 1994 to 30 September 1996, 1484 U.S. hospitals contributed patients to NRMI 2. Participation in the registry is voluntary. Registry hospitals are substantially larger than nonparticipating U.S. hospitals: Twenty-seven percent of registry hospitals have more than 350 beds compared with 8% of nonregistry hospitals. In addition, registry hospitals are more likely than nonregistry hospitals to be certified by the Joint Commission on Accreditation of Health Care Organizations (99% compared with 77%); be affiliated with a medical school (36% compared with 17%); and have a coronary care unit (73% compared with 31%), a cardiac catheterization laboratory (72% compared with 23%), and a cardiac surgery program (39% compared with 11%). Registry hospitals are encouraged to enter consecutive patients who have had acute myocardial infarction, regardless of treatment or outcome. Approval for hospital participation in the registry may include review by the local institutional review board or human research subjects committee as dictated by local policy. A study coordinator at each participating hospital completes individual data collection forms for each study patient; these forms are forwarded to an independent central data collection center (ClinTrials Research, Inc., Lexington, Kentucky) for processing. Data on individual hospitals are confidential and are available only to the contributing hospital. Patients Patients in our study had had acute myocardial infarction documented according to local hospital criteria (usually cardiac enzyme levels or results of electrocardiography or coronary angiography). For the purpose of our study, patients were those enrolled in NRMI 2 who received tPA as the initial reperfusion strategy from 1 June 1994 to 30 September 1996. To be eligible for study inclusion, patients could not have been transferred to a participating registry hospital from any other hospital (registry or otherwise) in the context of management of the acute myocardial infarction event. In addition, study patients could not have received a second dose of any thrombolytic agent. As of 30 September 1996, NRMI 2 included 389 130 patients. Of these, 99 694 had received tPA as the initial reperfusion strategy; 26 370 of these patients had been transferred from another hospital for treatment of acute myocardial infarction. Of the remaining 73 324 patients, 2115 had received a second dose of a thrombolytic agent and 136 patients had missing information on age or sex. This left 71 073 patients in the study sample. The number of study patients contributed per registry hospital ranged from 1 to 311. Definitions The occurrence of primary intracranial hemorrhage was indicated on the registry data collection form, along with the date and time of onset of neurologic symptoms and whether computed tomography or magnetic resonance imaging (MRI) was performed to confirm the event. Events reported to have been confirmed by computed tomography or MRI were of principal interest in our study. The time between administration of tPA and intracranial hemorrhage was calculated. Sequelae of intracranial hemorrhage were characterized as death during hospitalization, residual deficit at discharge, or no residual deficit at discharge. The magnitude of the residual deficit was not classified. The reported intracranial hemorrhages and the circumstances surrounding them were not independently verified; information on these events was limited to that available on the data collection form provided by the participating hospitals. We characterized patients according to age (<65 years, 65 to 74 years, or 75 years), sex, and ethnicity (white, black, or other). Clinical characteristics included history of myocardial infarction, angina, congestive heart failure, coronary artery bypass graft or percutaneous transluminal coronary angioplasty, stroke, diabetes mellitus, hypertension, hypercholesterolemia, and smoking. Systolic and diastolic blood pressure were characterized according to the first measurement recorded at hospital presentation. Likewise, Killip class was measured at presentation (no evidence of congestive heart failure, presence of rales or jugular venous distention, pulmonary edema, or cardiogenic shock) [10]. The study sample was stratified into quartiles according to body weight (measured in kg). The dose of tPA administered was categorized as less than 1.5 mg/kg or 1.5 mg/kg or more. These categories were based on manufacturer recommendations for tPA dosing [11]. (For patients weighing >67 kg, the maximum recommended total tPA dose is 100 mg [ 1.49 mg/kg]. Dosage adjustments based on weight are advised for patients weighing 67 kg or less.) Duration of tPA infusion was categorized as 90 minutes or less (accelerated tPA) or more than 90 minutes. We also characterized patients according to use of aspirin or intravenous heparin, which may be relevant to risk for bleeding. Statistical Analysis To assess comparability with a large clinical trial population, selected characteristics of our study sample were compared with those of patients who received accelerated tPA plus intravenous heparin in the GUSTO-I trial [5]. For our study sample, we evaluated the bivariate association between intracranial hemorrhage and selected demographic and clinical patient characteristics. These variables were used to develop stepwise multivariable logistic regression models with the occurrence of intracranial hemorrhage (confirmed by computed tomography or MRI) as the dependent variable. Patients with unknown values for any variable were excluded from multivariable analyses. The models were constructed with an entry significance level of P = 0.01 and an exit significance level of P = 0.05. Estimated odds ratios for the risk for intracranial hemorrhage, adjusted for all remaining variables, were obtained by using this model. Interactions between patient age and all other variables remaining in the final regression model were assessed. The goodness-of-fit criteria of Hosmer and Lemeshow were assessed for all models [12]. In addition, we calculated an area under the receiver-operating characteristic curve for each model [13]. All tests of statistical significance were two-tailed; a P value less than 0.05 was considered statistically significant. Multiple logistic regression analyses were performed by using the SAS PROC LOGISTIC procedure in SAS, version 6 (SAS Institute, Inc., Cary, North Carolina). The main-effects models were refit by using SAS PROC PHREG to control for potential int

The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) Trial

Background: Transcranial Doppler ultrasound (TCD) and magnetic resonance angiography (MRA) can identify intracranial atherosclerosis but have not been rigorously validated against the gold standard, catheter angiography. The WASID trial (Warfarin Aspirin Symptomatic Intracranial Disease) required performance of angiography to verify the presence of intracranial stenosis, allowing for prospective evaluation of TCD and MRA. The aims of Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial were to define abnormalities on TCD/MRA to see how well they identify 50 to 99% intracranial stenosis of large proximal arteries on catheter angiography. Study Design: SONIA standardized the performance and interpretation of TCD, MRA, and angiography. Study-wide cutpoints defining positive TCD/MRA were used. Hard copy TCD/MRA were centrally read, blind to the results of angiography. Results: SONIA enrolled 407 patients at 46 sites in the United States. For prospectively tested noninvasive test cutpoints, positive predictive values (PPVs) and negative predictive values (NPVs) were TCD, PPV 36% (95% CI: 27 to 46); NPV, 86% (95% CI: 81 to 89); MRA, PPV 59% (95% CI: 54 to 65); NPV, 91% (95% CI: 89 to 93). For cutpoints modified to maximize PPV, they were TCD, PPV 50% (95% CI: 36 to 64), NPV 85% (95% CI: 81 to 88); MRA PPV 66% (95% CI: 58 to 73), NPV 87% (95% CI: 85 to 89). For each test, a characteristic performance curve showing how the predictive values vary with a changing test cutpoint was obtained. Conclusions: Both transcranial Doppler ultrasound and magnetic resonance angiography noninvasively identify 50 to 99% intracranial large vessel stenoses with substantial negative predictive value. The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis trial methods allow transcranial Doppler ultrasound and magnetic resonance angiography to reliably exclude the presence of intracranial stenosis. Abnormal findings on transcranial Doppler ultrasound or magnetic resonance angiography require a confirmatory test such as angiography to reliably identify stenosis.

Stroke in children and sickle-cell disease Baltimore-Washington Cooperative Young Stroke Study

Background/Purpose: The Baltimore-Washington Cooperative Young Stroke Study is the largest biracial urban-suburban population-based study to examine the etiology of strokes in children. Methods: We identified all children aged 1 to 14 years discharged from all 46 hospitals in central Maryland and Washington, DC with a diagnosis of ischemic stroke and intracerebral hemorrhage in the years 1988 and 1991. Each medical record was reviewed by two neurologists for appropriateness of the diagnosis of stroke and for information on the patients history, clinical presentation, pertinent investigations, hospital stay, and outcome at time of discharge. Results: Eighteen children with ischemic infarction and 17 with intracerebral hemorrhage were identified. The most common cause of ischemic stroke was sickle-cell disease (39%), followed by vasculopathic (33%) and indeterminate(28%) causes. Causes of intracerebral hemorrhages were arteriovenous malformation (29%), hematologic (23%), vasculopathy (18%), surgical complication (12%), coagulopathy (6%), and indeterminate (12%). The overall incidence for childhood stroke was 1.29 per 100,000 per year, with ischemic stroke occurring at a rate of 0.58 per 100,000 and intracerebral hemorrhage occurring at a rate of 0.71 per 100,000. The incidence of stroke among children with sickle-cell disease was estimated to be 0.28% or 285 per 100,000 per year. Conclusion: Sickle-cell disease plays a disproportionately high role in childhood stroke when a biracial population is surveyed.