Electrocardiographic Correlates of Acute Allograft Rejection Among Heart Transplant Recipients.

BACKGROUND: Acute allograft rejection appears to be associated with increases in QT/QTc intervals. OBJECTIVES: To determine the relationship between acute allograft rejection and electrocardiogram changes in patients undergoing an orthotopic heart transplant. METHODS: The study population comprised 220 adult patients undergoing heart transplant and enrolled in the NEW HEART study. Electrocardiograms obtained within 72 hours of endomyocardial biopsy were analyzed; electrocardiograms obtained fewer than 10 days after transplant surgery were excluded. Repeated-measures analysis was performed with statistical models including effects for rejection severity (mild and moderate/severe) and time trends independent of rejection status. RESULTS: The 151 male and 69 female transplant recipients (mean age [SD], 54 [13] years) had 969 biopsy/electrocardiogram pairs: 677 with no rejection, 280 with mild rejection, and 12 with moderate/severe rejection. Moderate to severe organ rejection was associated with significant increases in QRS duration (P < .001), QT (P = .009), QTc (P = .003), and PR interval (P = .03), as well as increased odds of right bundle block branch (P = .002) and fascicular block (P = .009) occurring. CONCLUSIONS: Moderate to severe acute allograft rejection was associated with electrocardiographic changes after transplant surgery. Studies are needed to assess the value of computerized electrocardiogram measurement algorithms for detecting acute allograft rejection.

Clinical and gender differences in heart transplant recipients in the NEW HEART study.

BACKGROUND: Little attention has focused on gender differences in cardiac comorbidities and outcomes in patients undergoing orthotropic heart transplant. OBJECTIVE: The objective of this study was to investigate gender differences at baseline and during follow-up among heart transplant patients. METHODS: An observational cohort within the NEW HEART study was evaluated to determine gender differences in relation to age, coexisting cardiac comorbidities, and outcomes. Differences were assessed by t-test, Fisher's exact test, and logistic regression analysis. RESULTS: Male transplant recipients ( n = 238) were significantly older than female recipients ( n = 92), with a greater percentage over 60 years of age (45% vs. 24%, p = 0.0006). Males were more likely to have hypertension (63% vs. 49%, p = 0.034), dyslipidemia (62% vs. 45%, p = 0.006), a history of smoking (52% vs. 35%, p = 0.009), and diabetes (42% vs. 21%, p = 0.0002). Analysis of endomyocardial biopsies obtained during the 1-year follow-up period demonstrated that women averaged more episodes of acute rejection than men (3.9 vs. 3.0, p = 0.009). While most episodes of rejection were mild, women were more likely than men to have episodes of moderate or severe rejection (14% vs. 5%, p = 0.012) and to be hospitalized for acute rejection (15% vs. 6%, p = 0.013). There were no significant differences in mortality. CONCLUSIONS: Men were more likely than women to be older and to have diabetes, dyslipidemia, hypertension, and a history of smoking. Women were more likely to experience moderate or severe allograft rejection and to be hospitalized for acute rejection. Future investigation of the reasons for these gender differences is warranted and may improve clinical care of women undergoing cardiac transplantation.

Cardiovascular Disease Risk Among Young Urban Women.

BACKGROUND: Although young women are presumed to have low cardiovascular disease (CVD) risk and mortality, the mortality benefits secondary to ischemic heart disease have plateaued among young women, <50 years. MATERIALS AND METHODS: Women, 18-49 years (n = 595) among all participants (n = 1,045) in the Columbia University Heart Health in Action Study, were assessed for CVD risk burden, that is, presence of hypertension, diabetes mellitus, current tobacco use, hyperlipidemia, physical inactivity, and/or obesity. Anthropometrics (height, weight, waist circumference, and body mass index [BMI]); demographics; socioeconomic status, CVD risk factors, body size perception; knowledge and awareness of CV disease; and attitudes toward lifestyle perception were determined. RESULTS: Most were Hispanic (64.0%); non-Hispanic white (20.0%); or non-Hispanic black (8.7%), age = 35.9 ± 8.0 years. BMI was categorized as obese (≥30 kg/m2, 27.0%; 160/592); overweight (25.0-29.1 kg/m2, 29.1%; 172/592); normal weight (18.5-24.9, 41.7%; 247/592); and underweight (≤18.4; 2.2%; 13/592). More than half (57.9%; 337/582) had CVD risks: 45.9% (267/582) had >1 CVD risk factor exclusive of obesity, including physical inactivity (18.4%), hypertension (17.2%), hyperlipidemia (11.3%), current tobacco use (9.8%), and diabetes (5.6%). Regardless of CVD risk burden, most knew blood pressure, blood sugar, and cholesterol. Women with increased CVD risk burden, however, were less likely to correctly identify body size (53.3% vs. 66.1%, p = 0.002). Obese and overweight women with CVD risk factors exclusive of obesity were more likely to cite cost (23.4% vs. 10.7%, p = 0.003) and fatigue (32.2% vs. 18.8%, p = 0.006) as barriers to weight loss. CONCLUSION: Among these young women, the majority had CVD risks and the CVD risk burden is high among young women, particularly among the overweight and obese and physically inactive. Strategies to encourage healthy lifestyles and reduce CVD risk factors among this vulnerable at-risk population are vital.

The DHHS Office on Women's Health Initiative to Improve Women's Heart Health: focus on knowledge and awareness among women with cardiometabolic risk factors.

UNLABELLED: Abstract Background: The diversity of the U.S. population and disparities in the burden of cardiovascular disease (CVD) require that public health education strategies must target women and racial/ethnic minority groups to reduce their CVD risk factors, particularly in high-risk communities, such as women with the metabolic syndrome (MS). METHODS: The data reported here were based on a cross-sectional face-to-face survey of women recruited from four participating sites as part of the national intervention program, Improving, Enhancing and Evaluating Outcomes of Comprehensive Heart Care in High-Risk Women. Measures included baseline characteristics, sociodemographics, CVD related-knowledge and awareness, and Framingham risk score (FRS). RESULTS: There were 443 of 698 women (63.5%) with one or more risk factors for the MS: non-Hispanic white (NHW), 51.5%; non-Hispanic black (NHB), 21.0%; Hispanic, 22.6%. Greater frequencies of MS occurred among Hispanic women (p<0.0001), those with less than a high school education (70.0%) (p<0.0001), Medicaid recipients (57.8%) (p<0.0001), and urbanites (43.3%) (p<0.001). Fewer participants with MS (62.6%) knew the leading cause of death compared to those without MS (72.1%) (p<0.0001). MS was associated with a lack of knowledge of the composite of knowing the symptoms of a heart attack plus the need to call 911 (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.17-0.97, p=0.04). CONCLUSIONS: Current strategies to decrease CVD risk are built on educating the public about traditional factors, including hypertension, smoking, and elevated low-density lipoprotein cholesterol (LDL-C). An opportunity to broaden the scope for risk reduction among women with cardiometabolic risk derives from the observation that women with the MS have lower knowledge about CVD as the leading cause of death, the symptoms of a heart attack, and the ideal option for managing a CVD emergency.

Efficacy of lamina terminalis fenestration in reducing shunt-dependent hydrocephalus following aneurysmal subarachnoid hemorrhage: a systematic review. Clinical article.

OBJECT: Chronic hydrocephalus requiring shunt placement is a common complication following aneurysmal subarachnoid hemorrhage (SAH). Controversy exists over whether microsurgical fenestration of the lamina terminalis during aneurysm surgery affords a reduction in the development of shunt-dependent hydrocephalus. To resolve this debate, the authors performed a systematic review and quantitative analysis of the literature to determine the efficacy of lamina terminalis fenestration in reducing aneurysmal SAH-associated shunt-dependent hydrocephalus. METHODS: A MEDLINE (1950-2007) database search was performed using the following keywords, singly and in combination: "ventriculoperitoneal shunt," "hydrocephalus," "subarachnoid hemorrhage," "aneurysm," "fenestration," and "lamina terminalis." Additional studies were manually singled out by scrutinizing references from identified manuscripts, major neurosurgical journals and texts, and personal files. A recent study from the authors' institution was also incorporated into the review. Data from included studies were analyzed using the chi-square analysis and Student t-test. The Cochran-Mantel-Haenszel test was used to compare overall incidence of shunt-dependent hydrocephalus. RESULTS: The literature search revealed 19 studies, but only 11 were included in this review, involving 1973 patients. The fenestrated and nonfenestrated cohorts (combined from the various studies) differed significantly with regard to patient sex, age, and clinical grade as well as aneurysm location (p=0.0065, 0.0028, 0.0003, and 0.017, respectively). The overall incidence of shunt-dependent hydrocephalus in the fenestrated cohort was 10%, as compared with 14% in the nonfenestrated cohort (p=0.089). The relative risk of shunt-dependent hydrocephalus in the fenestrated cohort was 0.88 (95% CI 0.62-1.24). CONCLUSIONS: This systematic review revealed no significant association between lamina terminalis fenestration and a reduced incidence of shunt-dependent hydrocephalus. The interpretation of these results, however, is restricted by unmatched cohort differences as well as other inherent study limitations. Although the overall literature supports lamina terminalis fenestration, a number of authors have questioned the technique's benefits, thus rendering its efficacy in reducing shunt-dependent hydrocephalus unclear. A well-designed, multicenter, randomized controlled trial is needed to definitively address the efficacy of this microsurgical technique.

Inducible nitric oxide synthase promoter polymorphism affords protection against cognitive dysfunction after carotid endarterectomy.

BACKGROUND AND PURPOSE: Cognitive dysfunction occurs in 9% to 23% of patients during the first month after carotid endarterectomy (CEA). A 4-basepair (AAAT) tandem repeat polymorphism (either 3 or 4 repeats) has been described in the promoter region of inducible nitric oxide synthase (iNOS), a gene with complex roles in ischemic injury and preconditioning against ischemic injury. We investigated whether the 4-repeat variant (iNOS(+)) affects the incidence of cognitive dysfunction after CEA. METHODS: One-hundred eighty-five CEA and 60 spine surgery (control) subjects were included in this nested cohort analysis. Subjects underwent a battery of 7 neuropsychometric tests before and 1 day and 1 month after surgery. Multivariate logistic regression analyses were performed to determine if the iNOS promoter variant was independently associated with the incidence of cognitive dysfunction at 1 day and 1 month. Further, all right-hand-dominant CEA subjects were grouped by operative side and performance on each test was compared between iNOS(+) and iNOS(-) groups. RESULTS: Forty-four of 185 CEA subjects had at least 1 iNOS promoter allele containing 4 copies of the tandem repeat (iNOS(+)). iNOS(+) status was significantly protective against moderate/severe cognitive dysfunction 1 month after CEA. Right-hand-dominant iNOS(+) CEA subjects undergoing left-side CEA performed significantly better than iNOS(-) subjects on a verbal learning test and those undergoing right-side CEA performed significantly better on a test of visuospatial function. CONCLUSIONS: We demonstrate an iNOS promoter polymorphism variant provides protection against moderate/severe cognitive dysfunction 1 month after CEA. Further, this protection appears to involve cognitive domains localized ipsilateral to the operative carotid artery.

The efficacy of direct extracranial-intracranial bypass in the treatment of symptomatic hemodynamic failure secondary to athero-occlusive disease: a systematic review.

OBJECTIVE: The 1985 International Extracranial-Intracranial (EC-IC) Bypass Trial failed to show a benefit following surgery in patients with varying degrees of angiographic ICA stenosis. More recent studies using modern technology to identify appropriate candidates, however, have generated promising findings. As a result, controversy exists regarding the role of this technique in the treatment of symptomatic athero-occlusive disease. To this end, we performed a systematic review and quantitative analysis of the literature to determine if a subset of patients with symptomatic hemodynamic failure secondary to athero-occlusive disease may benefit from direct EC-IC bypass. METHODS: We performed a MEDLINE (1985-2007) database search using the following keywords, singly and in combination: EC-IC bypass, hemodynamic failure and misery perfusion. Additional studies were identified manually by scrutinizing references from identified manuscripts, major neurosurgical journals and texts, and personal files. Our literature search divided studies into three categories: natural history of patients with stage I hemodynamic failure (16 studies, 2320 patients), natural history of patients with stage II hemodynamic failure (3 studies 163 patients), and outcomes of patients with hemodynamic failure treated by EC-IC bypass (23 studies 506 patients). RESULTS: Patients with severe stage I and stage II hemodynamic failure are at higher risk of cerebral infarction than those with mild disease (p=.014, OR 1.17-4.08 and p=0.10, OR 0.89-3.63, respectively). Additionally, patients with severe hemodynamic failure respond better to surgery than those with mild disease (p=0.03, OR 0.16-0.92). CONCLUSIONS: Patients with severe hemodynamic failure secondary to athero-occlusive disease appear to benefit from direct EC-IC bypass surgery. As a result, the conclusions of the 1985 International EC-IC Bypass Trial may not be applicable to this subset of patients. A randomized clinical trial involving this patient population is warranted.

Intraoperative magnesium infusion during carotid endarterectomy: a double-blind placebo-controlled trial.

OBJECT: Recent data from both experimental and clinical studies have supported the use of intravenous magnesium as a potential therapy in the setting of cerebral ischemia. This study assessed whether intraoperative magnesium therapy improves neuropsychometric testing (NPT) following carotid endarterectomy (CEA). METHODS: One hundred eight patients undergoing CEA were randomly assigned to receive placebo infusion or 1 of 3 magnesium-dosing protocols. Neuropsychometric testing was performed 1 day after surgery and compared with baseline performance. Assessment was also performed on a set of 35 patients concurrently undergoing lumbar laminectomy to serve as a control group for NPT. A forward stepwise logistic regression analysis was performed to evaluate the impact of magnesium therapy on NPT. A subgroup analysis was then performed, analyzing the impact of each intraoperative dose on NPT. RESULTS: Patients treated with intravenous magnesium infusion demonstrated less postoperative neurocognitive impairment than those treated with placebo (OR 0.27, 95% CI 0.10-0.74, p = 0.01). When stratified according to dosing bolus and intraoperative magnesium level, those who were treated with low-dose magnesium had less cognitive decline than those treated with placebo (OR 0.09, 95% CI 0.02-0.50, p < 0.01). Those in the high-dose magnesium group demonstrated no difference from the placebo-treated group. CONCLUSIONS: Low-dose intraoperative magnesium therapy protects against neurocognitive decline following CEA.

A study of cognitive dysfunction in patients having carotid endarterectomy performed with regional anesthesia.

BACKGROUND: In previous studies, we found that approximately 25% of patients having carotid endarterectomy with general anesthesia (CEA general) develop cognitive dysfunction compared with a surgical control Group 1 day and 1 mo after surgery. In this study, we tested the hypothesis that patients having CEA with regional anesthesia (CEA regional) will develop significant cognitive dysfunction 1 day after surgery compared with a control group of patients receiving sedation 1 day after surgery. We did not study persistence of dysfunction. METHODS: To test this hypothesis, we enrolled 60 patients in a prospective study. CEA regional was performed with superficial and deep cervical plexus blocks in 41 patients. The control group consisted of 19 patients having coronary angiography or coronary artery stenting performed with sedation. A control group is necessary to account for the "practice effect" associated with repeated cognitive testing. The patients from the CEA regional group were enrolled at New York Medical Center and the control group at Columbia-Presbyterian Medical Center. The cognitive performance of all patients was evaluated using a previously validated battery of neuropsychometric tests. Differences in performance, 1 day after compared with before surgery, were evaluated by both event-rate and group-rate analyses. RESULTS: On postoperative day 1, 24.4% of patients undergoing CEA regional had significant cognitive dysfunction, where "significant" was defined as a total deficit score > or =2 SD worse than the mean performance in the control group. CONCLUSIONS: Patients undergoing CEA regional had an incidence of cognitive dysfunction which was not different than patients having CEA general as previously published and compared with a contemporaneously enrolled group.

Racial/ethnic disparities in time to follow-up after an abnormal mammogram.

BACKGROUND: Although non-Hispanic white women have an increased risk of developing breast cancer, the disease-specific survival is lower for African American and Hispanic women. Little is known about disparities in follow-up after an abnormal mammogram. The goal of this study was to investigate potential disparities in follow-up after an abnormal mammogram. METHODS: A retrospective cohort study of 6722 women with an abnormal mammogram and documented follow-up from January 2000 through December 2002 was performed at an academic medical center in New York City. The outcome was the number of days between the abnormal mammogram and follow-up imaging or biopsy. Cox proportional hazards models were used to assess the effect of race/ethnicity and other potential covariates. RESULTS: The median number of days to diagnostic follow-up after an abnormal mammogram was greater for African American (20 days) and Hispanic (21 days) women compared with non-Hispanic white (14 days) women (p < 0.001). Racial/ethnic disparities remained significant in a multivariable model controlling for age, Breast Imaging Reporting and Data System (BIRADS) category, insurance status, provider practice location, and median household income. CONCLUSIONS: After an abnormal mammogram, African American and Hispanic women had longer times to diagnostic follow-up compared with non-Hispanic white women. Future efforts will focus on identifying the barriers to follow-up so that effective interventions may be implemented.

Altered coronary vasomotor function in young patients with systemic lupus erythematosus.

OBJECTIVE: Accelerated atherosclerosis is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Altered coronary microvascular function may act as a marker of changes that predispose to the development of significant coronary vascular disease. The purpose of this study was to compare coronary flow reserve (CFR) in a group of premenopausal women with SLE and a group of age-, sex-, and race-matched healthy control subjects. METHODS: Coronary flow velocity in 18 premenopausal women with SLE (mean +/- SD age 29.4 +/- 5.9 years) and 19 matched healthy controls (mean +/- SD age 28.2 +/- 4.3 years) was assessed by transthoracic Doppler echocardiography after an overnight fast. The CFR was calculated as the ratio of hyperemic to baseline coronary blood flow velocity in the left anterior descending coronary artery. Hyperemia was induced by intravenous administration of adenosine triphosphate. RESULTS: The mean +/- SD duration of SLE was 8.2 +/- 7.2 years (range 0.25-25 years), and the mean +/- SD score on the Systemic Lupus Erythematosus Disease Activity Index was 11.0 +/- 5.3 (range 4.0-21.0). Adequate recordings of flow velocity in the left anterior descending artery under both conditions were obtained using an ultrasound procedure in all study subjects. CFR was significantly lower in SLE patients as compared with control subjects (mean +/- SD 3.4 +/- 0.8 versus 4.5 +/- 0.5; P < 0.0001). CONCLUSION: These findings provide evidence that coronary vasomotor function is impaired in patients with SLE and support the notion that many of these young patients have subclinical coronary artery disease.

Preclinical evaluation of the neuroprotective effect of soluble complement receptor type 1 in a nonhuman primate model of reperfused stroke.

OBJECT: Postischemic cerebral inflammatory injury has been extensively investigated in an effort to develop effective neuroprotective agents. The complement cascade has emerged as an important contributor to postischemic neuronal injury. Soluble complement receptor Type 1 (sCR1), a potent inhibitor of complement activation, has been shown to reduce infarct volume and improve functional outcome after murine stroke. Given numerous high-profile failures to translate promising antiinflammatory strategies from the laboratory to the clinic and given the known species-specificity of the complement cascade, the authors sought to evaluate the neuroprotective effect of sCR1 in a nonhuman primate model of stroke. METHODS: A total of 48 adult male baboons (Papio anubis) were randomly assigned to receive 15 mg/kg of sCR1 or vehicle. The animals were subjected to 75 minutes of middle cerebral artery occlusion/reperfusion. Perioperative blood samples were analyzed for total complement activity by using a CH50 assay. Infarct volume and neurological scores were assessed at the time the animals were killed, and immunohistochemistry was used to determine cerebral drug penetration and C1q deposition. An interim futility analysis led to termination of the trial after study of 12 animals. Total serum complement activity was significantly depressed in the sCR1-treated animals compared with the controls. Immunostaining also demonstrated sCR1 deposition in the ischemic hemispheres of treated animals. Despite these findings, there were no significant differences in infarct volume or neurological score between the sCR1--and vehicle-treated cohorts. CONCLUSIONS: A preischemic bolus infusion of sCR1, the most effective means of administration in mice, was not neuroprotective in a primate model. This study illustrates the utility of a translational primate model of stroke in the assessment of promising antiischemic agents prior to implementation of large-scale clinical trials.

Preoperative prediction of long-term outcome in poor-grade aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To evaluate which presentation indices, demographics, and clinical information predict 12-month outcome in poor-grade aneurysmal subarachnoid hemorrhage (SAH), and to provide a preoperative index of prognosis. METHODS: Data were obtained on all patients with poor-grade (Hunt and Hess Grades IV and V) aneurysmal SAH from a prospectively maintained SAH database and health outcomes project. Demographics, medical history, presenting clinical condition, and health outcomes were analyzed. Survival analysis was performed and Kaplan-Meier curves were generated. Multivariable logistic regression analysis was used to identify significant predictors of poor outcome at 12 months after hemorrhage, as measured by the modified Rankin disability scale. RESULTS: Survival curves for open surgery and endovascular treatment did not differ significantly. Overall, 40% of the 98 definitively treated patients had a favorable outcome at 12 months. Multivariable analysis identified patient age older than 65 years (P < 0.001), hyperglycemia (P < 0.03), worst preoperative Hunt and Hess Grade V (P < 0.0001), and aneurysm size of at least 13 mm (P < 0.002) as significant predictors of poor outcome. These variables were weighted and used to compute a poor-grade aneurysmal SAH Prognosis Score (hereafter, Prognosis Score) for each patient. A Prognosis Score of 0 was associated with a 90% favorable outcome; Prognosis Score of 1 with 83%; Prognosis Score of 2 with 43%; Prognosis Score of 3 with 8%; Prognosis Score of 4 with 7%; and a Prognosis Score of 5 with 0%. CONCLUSION: Outcome in poor-grade aneurysmal SAH is strongly predicted by patient age, worst preoperative Hunt and Hess clinical grade, and aneurysm size. Hyperglycemia on admission after poor-grade aneurysmal SAH increases the likelihood of poor outcome, and is a potentially modifiable risk factor. The Prognosis Score is a useful tool for preoperatively assessing the likelihood of a favorable outcome for poor-grade aneurysmal SAH patients.

Left ventricular systolic dysfunction and the risk of ischemic stroke in a multiethnic population.

BACKGROUND AND PURPOSE: Left ventricular dysfunction (LVD) is associated with cardiovascular mortality. Its association with ischemic stroke has been mainly documented after myocardial infarction. The stroke risk associated with LVD, especially of mild degree, in the general population is unclear. The purpose of this study was to evaluate the relationship between LVD and ischemic stroke in a multiethnic cohort. METHODS: LV systolic function was assessed by transthoracic 2-dimensional echocardiography in a subset of subjects from the Northern Manhattan Study (NOMAS), 270 patients with first ischemic stroke and 288 age-, gender- and race-matched community controls. LV ejection fraction was measured by a simplified cylinder-hemiellipsoid formula, and categorized as normal (>50%), mildly (41% to 50%), moderately (31% to 40%) or severely (< or =30%) decreased. The association between impaired ejection fraction and ischemic stroke was evaluated by logistic regression analysis after adjustment for established stroke risk factors. RESULTS: LVD of any degree was more frequent in stroke patients (24.1%) than in controls (4.9%; P<0.0001), as was moderate/severe LVD (13.3% versus 2.4%; P<0.001). A decreased ejection fraction was associated with ischemic stroke even after adjusting for other stroke risk factors. The adjusted odds ratio for any degree of LVD was 3.92 (95% CI, 1.93 to 7.97). The adjusted odds ratio for mild LVD was 3.96 (95% CI, 1.56 to 10.01) and for moderate/severe LVD 3.88 (95% CI, 1.45 to 10.39). The association between LVD of any degree and stroke was present in all age, gender and race-ethnicity subgroups. CONCLUSIONS: LVD, even of mild degree, is independently associated with an increased risk of ischemic stroke. The assessment of LV function should be considered in the assessment of the stroke risk.

Predictors of neurocognitive decline after carotid endarterectomy.

OBJECTIVE: Although the incidence of stroke after carotid endarterectomy (CEA) is low (1-3%), approximately 25% of patients experience subtle declines in postoperative neuropsychometric function. No studies have investigated the risk factors for this neurocognitive change. We sought to identify predictors of postoperative neurocognitive dysfunction. METHODS: We enrolled 186 CEA patients, with both symptomatic and asymptomatic stenosis, to undergo a battery of neuropsychometric tests preoperatively and on postoperative Days 1 and 30. Neurocognitive dysfunction was defined as a two standard deviation decline in performance compared with a similarly aged control group of lumbar laminectomy patients. Univariate logistic regression was performed for age, sex, obesity, smoking, symptomatology, diabetes mellitus, hypertension, hypercholesterolemia, use of statin medication, previous myocardial infarction, previous CEA, operative side, duration of surgery, duration of carotid cross-clamp, and weight-adjusted doses of midazolam and fentanyl. Variables achieving univariate P < 0.10 were included in a multivariate analysis. Data is presented as (odds ratio, 95% confidence interval, P-value). RESULTS: Eighteen and 9% of CEA patients were injured on postoperative Days 1 and 30, respectively. Advanced age predicted neurocognitive dysfunction on Days 1 and 30 (1.93 per decade, 1.15-3.25, 0.01; and 2.57 per decade, 1.01-6.51, 0.049, respectively). Additionally, diabetes independently predicted injury on Day 30 (4.26, 1.15-15.79, 0.03). CONCLUSIONS: Advanced age and diabetes predispose to neurocognitive dysfunction after CEA. These results are consistent with risk factors for neurocognitive dysfunction after coronary bypass and major stroke after CEA, supporting an underlying ischemic pathophysiology. Further work is necessary to determine the role these neurocognitive deficits may play in appropriately selecting patients for CEA.

Neuropsychological dysfunction in the absence of structural evidence for cerebral ischemia after uncomplicated carotid endarterectomy.

OBJECTIVE: Neurocognitive dysfunction has been shown to occur in roughly 25% of patients undergoing carotid endarterectomy (CEA). Despite this, little is known about the mechanism of this injury. Recently, several groups have shown that new diffusion weighted imaging (DWI)-positive lesions are seen in 20% of patients undergoing CEA. We investigated to what degree neurocognitive dysfunction was associated with new DWI lesions. METHODS: Thirty-four consecutive patients undergoing CEA were subjected to pre- and postoperative cognitive evaluation with a battery of neuropsychological tests. Postoperative magnetic resonance imaging was performed in all patients within 24 hours of surgery. Lesions that showed high signal on DWI and restricted diffusion on apparent diffusion coefficient maps but no abnormal high signal on the fluid-attenuated inversion recovery images were considered hyperacute. RESULTS: Cognitive dysfunction was seen in eight (24%) patients. New hyperacute DWI lesions were seen in three (9%). Only one (13%) of the patients with cognitive dysfunction had a new DWI lesion. Two thirds of the new DWI lesions occurred in the absence of cognitive deterioration. Patients with cognitive dysfunction had significantly longer carotid cross-clamp times. CONCLUSION: Neurocognitive dysfunction after CEA does not seem to be associated with new DWI positive lesions.

Aortic valve calcification as an incidental finding at CT of the elderly: severity and location as predictors of aortic stenosis.

OBJECTIVE: The purpose of this study was to correlate the severity and location of aortic valve calcifications, as an incidental finding at chest CT of elderly persons, with pressure gradients across the valve. MATERIALS AND METHODS: One hundred fifteen subjects who were 60 years old or older and who showed aortic valve calcification on chest CT (5-mm reconstructed section width, no IV contrast material) and who had also undergone transthoracic echocardiography within 3 months of the CT examination were identified retrospectively. Aortic valve calcification scores (Agatston and volumetric) and subjective calcification pattern scores (based on a 9-point scale) were calculated and correlated with echocardiographic gradients. RESULTS: Thirty patients (26%) (median age, 81 years) were identified who showed an increased pressure gradient across the aortic valve at echocardiography. Eighty-five subjects (74%), including 30 age-matched but otherwise randomly selected control subjects, showed no increase in pressure gradient. The severity of aortic valve calcification was greater for the 30 subjects with an increased gradient than for the control subjects (p < 0.0001). Increased mean and peak gradients across the aortic valve correlated with the subjective scores for aortic valve calcification (r = 0.69 and 0.65, respectively; p < 0.0001), with Agatston scores (r = 0.76 and 0.70, respectively; p < 0.0001), and with volumetric scores (r = 0.78 and 0.73, respectively; p < 0.0001). In terms of specific commissures, the greatest correlation with mean and peak gradients was for peripheral left-posterior commissural calcification (r = 0.71 and 0.65, respectively; p < 0.0001) and central right-left commissural calcification (r = 0.69 and 0.66, respectively; p < 0.0001). CONCLUSION: The severity of aortic valve calcifications on chest CT, as assessed either subjectively or objectively, correlated with increased pressure gradients across the aortic valve, particularly for calcification of the peripheral left-posterior commissure and the central right-left commissure. These results indicate that the severity and location of aortic valve calcifications on chest CT are associated with an increased pressure gradient across the aortic valve.

Comparison of electrophysiologic monitors with clinical assessment of level of sedation.

OBJECTIVE: To assess the correlation between 2 clinical sedation scales and 2 electroencephalographic (EEG)-based monitors used during surgical procedures that required mild to moderate sedation. PATIENTS AND METHODS: Patients scheduled for elective surgery participated in this Institutional review board-approved study from March 2003 to February 2004. Level of sedation was determined both clinically using the Ramsay and the Observer's Assessment of Alertness/Sedation scales and with 2 EEG measures (the Bispectral Index version XP [BIS XP] or the Patient State Analyzer [PSA 4000]). Correlation between these 2 measures of sedation were tested using nonparametric statistical tests. RESULTS: The BIS XP monitor was used in 26 patients, and the PSA 4000 monitor was used in 24 patients. The Ramsay and Observer's Assessment of Alertness/Sedation scores correlated with each other (r = -0.96; P < .001) and with both the BIS XP (r = -0.89 and r = 0.91, respectively; P < .001) and the PSA 4000 (r = -0.80 and r = 0.80, respectively; P < .001) values. However, this correlation was strongest only at the extremes. Between the BIS XP and PSA 4000 values of 61 and 80, the clinical sedation scores varied greatly. CONCLUSION: On the basis of our results, these EEG-based monitors cannot reliably distinguish between light and deep sedation.

High dose magnesium infusions are not associated with increased pressor requirements after carotid endarterectomy.

INTRODUCTION: Although magnesium provides cerebral protection in animal stroke models, magnesium therapy has significant side effects in humans. Therefore, we sought to examine the incidence of alpha-agonist treated hypotension in our ongoing, prospective, randomized, double-blind, placebo-controlled Phase I/IIa dose escalation study of magnesium therapy in patients undergoing carotid endarterectomy. METHODS: Eighty patients undergoing elective carotid endarterectomy were randomly assigned to a placebo control group (n = 38) or to one of the three intravenous magnesium groups. Magnesium levels were obtained before induction, and then 15 minutes, 1 hour, 2 hours, 6 hours, 12 hours, and 24 hours after a loading dose and infusion. After surgery, a target systolic blood pressure range was chosen, and the amount and duration of phenylephrine needed to maintain that pressure was compared across treatment groups. RESULTS: All treatment groups achieved levels significantly different from baseline at 12 and 24 hours (P < 0.01). Magnesium treatment did not significantly increase the proportion of patients requiring pressure support. For those requiring pressure support, the amount and average duration of phenylephrine required was not different between control patients and those receiving magnesium, even when the individual minimum systolic blood pressures required were subdivided on the basis of dose of magnesium administered. CONCLUSION: There were no significant differences detected in the 1) percentage of patients requiring pressor support, 2) the duration of postoperative pressor support, or 3) the amount of phenylephrine support needed between controls and magnesium treated patients. The percentage of patients requiring pressure support depended on the minimum systolic blood pressure ordered after surgery.

Determinants of staged endovascular and surgical treatment outcome of brain arteriovenous malformations.

BACKGROUND AND PURPOSE: Therapy of brain arteriovenous malformations (AVMs) often requires the combination of different treatment modalities. Independently assessed data on neurologic outcome after multidisciplinary AVM therapy are scarce. METHODS: The 119 consecutive patients (49% women, mean age 34+/-13 years) with brain AVMs receiving endovascular embolization followed by surgical treatment were analyzed. Neurologic impairment was assessed prospectively by a neurologist using the modified Rankin Scale (mRS) before, during, and after completed AVM therapy. The association of demographic, clinical, and morphologic characteristics with new treatment-related neurologic deficits was calculated. RESULTS: The 119 patients were treated with 240 superselective embolizations (median, 2; range, 1 to 8) using n-butyl cyanoacrylate. Mean follow-up time after surgery was 9.6+/-13.2 months. On the Spetzler-Martin scale, 8% of the AVMs were grade 1, 27% grade 2, 40% grade 3, 22% grade 4, and 3% grade 5. Disabling treatment-related complications (mRS> or =3) occurred in 5% (95% confidence interval [CI], 1% to 9%) of the patients. Nondisabling new deficits were observed in another 42% (95% CI, 33% to 51%). No patient died. Nonhemorrhagic AVM presentation (odds ratio [OR], 5.00; 95% CI, 1.75 to 14.29), deep venous drainage (OR, 3.09; 95% CI, 1.43 to 6.64), AVM location in an eloquent brain region (OR, 2.42; 95% CI, 1.10 to 5.33), and large AVM size (OR, 1.05; 95% CI, 1.01 to 1.09) were independently associated with new treatment-related deficits. CONCLUSIONS: Our results suggest an increased treatment risk for patients with previously unbled AVMs from combined endovascular and surgical AVM therapy. Additional risk factors for treatment-related neurologic deficits may be large AVM size, deep venous drainage, and AVM location in eloquent brain regions.