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This study examined left-ventricular assist device (LVAD) patients with pre-LVAD ventricular arrhythmias (VAs) to determine the rate of recurrent post-LVAD VAs and the impact of pre-LVAD atrial fibrillation (AF) on recurrent post-LVAD VAs. Medical records of 195 consecutive LVAD patients were reviewed. Descriptive statistics were generated and Cox proportional hazard models were used to assess the association of clinical variables with the time to recurrent VA. Forty-seven percent of 195 CHF patients who received LVAD-manifested significant VAs prior to LVAD implant (82% Heartmate II, 14% HVAD, 4% other; median follow-up = 17 months), 41% of whom manifested recurrent post-LVAD VAs. Pre-LVAD AF was associated with recurrent VAs (hazard ratio = 3.73; 95% CI 1.33, 10.48; p = 0.012). Recurrent VAs were associated with increased mortality (hazard ratio = 3.06; 95% CI 1.17, 7.98; p = 0.023). A history of AF is prevalent in over half of LVAD patients with recurrent VAs and is associated with time to recurrence of VA.

There are limited studies evaluating whether atrial fibrillation (AF) patients with increased BMI, age, and left atrial (LA) size have altered intracardiac electrogram (EGM) morphology.We analyzed left atrial intracardiac EGMs acquired during invasive electrophysiology study in 54 patients with AF. EGM correlations were assessed among AF risk factors including age, left atrial size, and BMI.BMI correlated positively with DF (rEGM morphology of AF patients with increased BMI, older age, and an enlarged LA possessed decreased amplitude and decreased width and increased DF and MP. These findings suggest that atrial remodeling due to increased age, LA size, and BMI is associated with differences in local atrial activation, decreased refractoriness, and more heterogeneous activation. These novel findings point out clinical risk factors for atrial fibrillation that may affect electrogram characteristics.

Objective This study evaluated the impact of daily ECG (electrocardiogram) self‐recordings on time to documented recurrent atrial fibrillation (AF) or atrial flutter (AFL) and time to treatment of recurrent arrhythmia in patients undergoing catheter radiofrequency ablation (RFA) or direct current cardioversion (DCCV) for AF/AFL. Background AF recurrence rates after RFA and DCCV are 20% to 45% and 60% to 80%, respectively. Randomized trials comparing mobile ECG devices to standard of care have not been performed in an AF/AFL population after treatment. Methods Of 262 patients consented, 238 were randomized to either standard of care (123) or to receive the iHEART intervention (115). Patients in the intervention group were provided with and trained to use an AliveCor KardiaMobile ECG monitor, and were instructed to take and transmit daily ECG recordings. Data were collected from transmitted ECG recordings and patients’ electronic health records. Results In a multivariate Cox model, the likelihood of recurrence detection was greater in the intervention group (hazard ratio = 1.56, 95% confidence interval [CI]: 1.06‐2.30, P = .024). Hazard ratios did not differ significantly for RFA and DCCV procedures. Recurrence during the first month after ablation strongly predicted later recurrence (hazard ratio = 4.53, 95% CI: 2.05‐10.00, P = .0006). Time from detection to treatment was shorter for the control group (hazard ratio = 0.33, 95% CI: 0.57‐2.92, P

Little attention has focused on gender differences in cardiac comorbidities and outcomes in patients undergoing orthotropic heart transplant.The objective of this study was to investigate gender differences at baseline and during follow-up among heart transplant patients.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.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.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.

Author(s): Hickey, Kathleen T; Sciacca, Robert R; Chen, Belinda; Drew, Barbara J; Pickham, David; Carter, Erik V; Castillo, Carmen; Doering, Lynn V | Abstract: 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 l .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.

Aims and objectives To determine the relationship between quality of life and perceived self-reported symptoms in an older, ambulatory, urban population living with heart failure. Background While arrhythmias in older individuals with heart failure are well documented, the association between perceived arrhythmia symptoms and quality of life is not well-defined. Design Prospective, cross-sectional single-centre study. Methods A single-centre, prospective study was conducted with heart failure patients recruited from an urban outpatient cardiology clinic in the United States. Fifty-seven patients completed a baseline quality of life survey with 42 of these completing the six-month follow-up survey. Quality of life was evaluated with the SF-36v2™ and frequency of symptoms with the Atrial Fibrillation Severity Scale. Subjects wore an auto triggered cardiac loop monitor (LifeStar AF Express®) for two weeks to document arrhythmias. Data analysis utilised Spearman's rank correlation and logistic regression. Results Baseline and six-month quality of life measures did not correlate with recorded arrhythmias. However, perceptions of diminished general health correlated significantly with symptoms of exercise intolerance, lightheadedness/dizziness, palpitations and chest pain/pressure. By multivariable logistic regression, more severe perceived episodes, symptoms of exercise intolerance and lightheadedness/dizziness were independently associated with diminished quality of life. Conclusion Quality of life was significantly worse in patients with perceptions of severe arrhythmic episodes and in those with symptoms of dizziness and exercise intolerance. Relevance to clinical practice The findings of this study indicate that symptomatic heart failure patients suffer from poor quality of life and that interventions are needed to improve quality of life and decrease symptom severity. Nurses who care for heart failure patients play an essential role in symptom evaluation and management and could significantly improve overall quality of life in these patients by carefully evaluating symptomatology and testing interventions and educational programmes aimed at improving quality of life.

Although many scales attempt to predict outcome following aneurysmal subarachnoid hemorrhage (aSAH), none have achieved universal acceptance, and most scales in common use are not statistically derived. We propose a statistically validated scale for poor grade aSAH patients that combines the Hunt and Hess grades and the Glasgow Coma Scale (GCS) scores; we refer to this as the Poor Grade GCS (PGS). The GCS scores of 160 poor grade aSAH patients (Hunt and Hess Grades 4 and 5) were recorded throughout their hospital stay. Outcomes were assessed by the modified Rankin scale (mRS). Analysis of variance and the Chi-square test were used to guide an analysis of GCS breakpoints according to outcomes. Multivariable logistic regression analysis was used to assess the ability of the Hunt and Hess, GCS, World Federation of Neurological Surgeons Grading Scale, and the PGS to predict long-term outcome. Outcome analysis revealed significant breakpoints in admission GCS scores: PGS-A (GCS 10-12); PGS-B (GCS 8-9); PGS-C (GCS 5-7); PGS-D (GCS 3-4) (p

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. Conclusion— 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.

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.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.On postoperative day 1, 24.4% of patients undergoing CEA regional had significant cognitive dysfunction, where "significant" was defined as a total deficit scoreor =2 SD worse than the mean performance in the control group.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.

Object Despite efforts to elucidate both the molecular mechanism and the clinical predictors of vasospasm after aneurysmal subarachnoid hemorrhage (ASAH), its pathogenesis remains unclear. Monocyte chemoattractant protein–1 (MCP-1) is a chemokine that has been firmly implicated in the pathophysiology of vasospasm and in neural tissue injury following focal ischemia in both animal models and human studies. The authors hypothesized that MCP-1 would be found in increased concentrations in the blood and cerebrospinal fluid (CSF) of patients with ASAH and would correlate with both outcome and the occurrence of vasospasm. Methods Seventy-seven patients who presented with ASAH were prospectively enrolled in this study between July 2001 and May 2002. Using an enzyme-linked immunosorbent assay, MCP-1 levels were measured in serum daily and in CSF when available. The mean serum and CSF MCP-1 concentrations were calculated for each patient throughout the entire hospital stay. Neurological outcome was evaluated at discharge or 14 days posthemorrhage using the modified Rankin Scale. Vasospasm was evaluated on angiography. Results The serum MCP-1 concentrations correlated with negative outcome such that a 10% increase in concentration predicted a 25% increase in the probability of a poor outcome, whereas the serum MCP-1 levels did not correlate with vasospasm. Concentrations of MCP-1 in the CSF, however, proved to be significantly higher in patients with angiographically demonstrated vasospasm. Conclusions These findings suggest a role for MCP-1 in neurological injury and imply that it may act as a biomarker of poor outcome in the serum and of vasospasm in the CSF.

BACKGROUND: Noninvasive and accurate assessment of mitral valve anatomy has become integral in the presurgical evaluation of patients with mitral valve prolapse (MVP). Recently developed real time three-dimensional (RT3D) ultrasound allows online acquisition, rendering, and can provide accurate information on cardiac structures. We sought to evaluate the feasibility of RT3D for the assessment of MVP segments when compared with transesophageal echocardiography (TEE) and intraoperative findings. METHODS: We examined 42 patients with MVP using RT3D, two-dimensional (2D) transthoracic echocardiography (TTE) and TEE. For RT3D analysis, cropping planes were used to slice the 3D volume on line to visualize the prolapsed segments of the mitral valve leaflets. The mitral valve was divided into six segments based on the American Society of Echocardiography's recommendations. Two experienced cardiologists evaluated echocardiographic images. RESULTS: Adequate RT3D images of the mitral valve were acquired in 40 out of 42 patients. The sensitivity and specificity of RT3D for defining prolapsed segments when compared with TEE were 95% and 99%, respectively (anterior leaflet: 96% and 99%, posterior leaflets: 93% and 100%, respectively). The sensitivity and specificity of TTE were 93% and 97%, respectively (anterior leaflet: 96% and 98%, posterior leaflets: 90% and 97%, respectively). Interobserver agreement for RT3D (Kappa 0.95, 95% confidence interval [CI] 0.91-1.00) was significantly greater than for TTE (Kappa 0.85, 95% CI 0.78-0.93) (P < 0.05). The elapsed time for completion of RT3D (14.4 +/- 2.8 min) was shorter than for TEE (26.4 +/- 4.7 min, P < 0.0001) and TTE (19.0 +/- 3.1 min, P< 0.0001). CONCLUSIONS: RT3D is fast, accurate, and highly reproducible for assessing MVP.

Objectives We sought to assess the risk of ischemic stroke from a patent foramen ovale (PFO) in the multiethnic prospective cohort of northern Manhattan. Background Patent foramen ovale has been associated with increased risk of ischemic stroke, mainly in case-control studies. The actual PFO-related stroke risk in the general population is unclear. Methods The presence of PFO was assessed at baseline by using transthoracic 2-dimensional echocardiography with contrast injection in 1,100 stroke-free subjects older than 39 years of age (mean age 68.7 +/- 10.0 years) from the Northern Manhattan Study (NOMAS). The presence of atrial septal aneurysm (ASA) also was recorded. Subjects were followed annually for outcomes. We assessed PFO/ASA-related stroke risk after adjusting for established stroke risk factors. Results We detected PFO in 164 subjects (14.9%); ASA was present in 27 subjects (2.5%) and associated with PFO in 19 subjects. During a mean follow-up of 79.7 +/- 28.0 months, an ischemic stroke occurred in 68 subjects (6.2%). After adjustment for demographics and risk factors, PFO was not found to be significantly associated with stroke (hazard ratio 1.64, 95% confidence interval [CI] 0.87 to 3.09). The same trend was observed in all age, gender, and race-ethnic subgroups. The coexistence of PFO and ASA did not increase the stroke risk (adjusted hazard ratio 1.25, 95% CI 0.17 to 9.24). Isolated ASA was associated with elevated stroke incidence (2 of 8, or 25%; adjusted hazard ratio 3.66, 95% CI 0.88 to 15.30). Conclusions Patent foramen ovale, alone or together with ASA, was not associated with an increased stroke risk in this multiethnic cohort. The independent role of ASA needs further assessment in appositely designed and powered studies.

This study sought to determine the prevalence of atrial fibrillation (AF) and its association with cardiac outcomes in patients with left ventricular assist devices (LVADs).LVADs are pivotal treatments for end-stage heart failure and a critical bridge to heart transplantation.Medical records of 249 consecutive patients who received an LVAD at Columbia University Medical Center were reviewed. Patient demographics, clinical variables, medications, and outcomes were recorded. Descriptive statistics were generated, and multivariable logistic regression was performed to assess the independent association of clinical variables with the presence of AF.Overall, AF was documented in 80 patients (32%) following LVAD placement. Before LVAD placement, 182 patients had no history of AF, whereas 67 patients had documented AF. Among these 67 patients, 56 (84%) continued to have AF following LVAD placement; 24 patients without a history of AF (13%) developed AF after LVAD placement. Patients manifesting AF after LVAD placement were more likely to have had AF before LVAD insertion (p 0.001). There were no significant differences in risk of stroke or death for patients with AF before or following LVAD insertion.AF is common in patients with LVADs, with 32% manifesting AF after placement of their LVAD, including 13% without a prior documented history of AF. The presence of AF was not associated with increased risk of death or stroke.

The presence of subclinical cardiovascular disease has been documented to indicate high coronary risk. This study investigated the impact of subclinical cardiovascular disease derived from echocardiography and carotid ultrasonography on traditional coronary risk stratification using the Framingham risk score (FRS) in a community-based, multiethnic population. Echocardiography and carotid ultrasonography were performed in 1,445 subjects (aged >39 years; 40% men; 53% Hispanic, 20% white, 24% black) from the Northern Manhattan Study. Subclinical cardiovascular disease was defined as the presence of left ventricular hypertrophy and/or carotid plaque greater than the gender-specific 75th percentile of the left ventricular mass index and maximal carotid plaque thickness distribution. The prevalence of subclinical cardiovascular disease was examined in each FRS category (low, intermediate, and high risk). In subjects with low or intermediate FRSs, 35% had subclinical cardiovascular disease (low FRS 29%, intermediate FRS 42%). In the intermediate FRS category, subclinical cardiovascular disease was significantly more prevalent in women than in men (53% vs 32%, p

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.

Background: Intracranial hemorrhage is a serious possible complication in patients with brain arteriovenous malformation (AVM). Several morphologic factors associated with hemorrhagic AVM presentation have been established, but their relevance for the risk of subsequent AVM hemorrhage remains unclear. Methods: The authors analyzed follow-up data on 622 consecutive patients from the prospective Columbia AVM database, limited to the period between initial AVM diagnosis and the start of treatment (i.e., any endovascular, surgical, or radiation therapy). Univariate and multivariate logistic regression and Cox proportional hazard models were applied to analyze the effect of patient age, gender, AVM size, anatomic location, venous drainage pattern, and associated arterial aneurysms on the risk of intracranial hemorrhage at initial presentation and during follow-up. Results: The mean pretreatment follow-up was 829 days (median: 102 days), during which 39 (6%) patients experienced AVM hemorrhage. Increasing age (hazard ratio [HR] 1.05, 95% CI 1.03 to 1.08), initial hemorrhagic AVM presentation (HR 5.38, 95% CI 2.64 to 10.96), deep brain location (HR 3.25, 95% CI 1.30 to 8.16), and exclusive deep venous drainage (HR 3.25, 95% CI 1.01 to 5.67) were independent predictors of subsequent hemorrhage. Annual hemorrhage rates on follow-up ranged from 0.9% for patients without hemorrhagic AVM presentation, deep AVM location, or deep venous drainage to as high as 34.4% for those harboring all three risk factors. Conclusions: Hemorrhagic arteriovenous malformation (AVM) presentation, increasing age, deep brain location, and exclusive deep venous drainage appear to be independent predictors for AVM hemorrhage during natural history follow-up. The risk of spontaneous hemorrhage may be low in AVMs without these risk factors.

Bispectral Index (BIS) has been used to monitor level of “sedation” based on the electroencephalogram (EEG). Patients evaluated for surgery to control a seizure disorder undergo Wada testing, during which one hemisphere is rendered functionally inactive after injecting a short-acting barbiturate. We surmised that the BIS values would reflect these functional changes. Eight epileptic patients were enrolled. A full array of 21 EEG electrodes and 2 BIS XP (Quatro) strips over each frontal region of the scalp were applied. The EEG was continuously recorded. BIS values from each hemisphere were recorded every minute. Angiography was performed by advancing a catheter into each internal carotid artery. Amobarbital or methohexital was injected until the patient developed a hemiparesis. The EEG confirmed a significant lateralized cortical effect of the barbiturate. Repeated measures analysis of variance was used to analyze the differences between the BIS values from monitor electrode strips placed on the left (left BIS) and the right (right BIS) sides of the head as well as the differences in the left and right BIS values before and after each injection of the barbiturate. Injection of barbiturate into either the left or right internal carotid artery produced a significant change on the 21-electrode EEG. However, there was no difference between left BIS to right BIS values (P = 0.84). With repeated injections of barbiturates, some patients became sedated. At these times, both left BIS and right BIS values decreased together before and after injection of barbiturate. The BIS monitor was unable to distinguish significant hemispheric EEG and clinical functional changes except when the patient became sedated.

Background Oxygen 15 water and nitrogen 13 ammonia are widely used for the quantitative measurement of myocardial perfusion with positron emission tomography. However, blood flow obtained with N-13 ammonia by use of the conventional 2-compartment model frequently underestimates flow by 30% to 50% compared with O-15 water. We hypothesized that this discrepancy is a result of the model configuration of N-13 ammonia and investigated changes to the mathematical model to determine whether more accurate measurements of perfusion could be obtained. Methods and Results Twelve healthy volunteers were sequentially studied with O-15 water and N-13 ammonia at rest and during maximal coronary vasodilation with adenosine. Perfusion measurements obtained with the conventional and modified models were compared with values obtained with O-15 water. The conventional N-13 ammonia model underestimated flow by 37% ± 16% at rest and by 20% ± 24% with stress when compared with flows obtained with O-15 water. The modified model yielded flow values closer to the line of identity than the conventional model (y = 1.07x + 0.04 vs y = 0.69x + 0.08; respectively; P Conclusions Model changes made N-13 ammonia myocardial blood flow estimates more comparable to those obtained with O-15 and may allow for better comparison of flows obtained with these two tracers in the future. Further efforts are warranted to evaluate the accuracy of flow models in human subjects.

To show that serum interleukin levels are associated with carotid intima-media thickness (IMT).Inflammation is hypothesized to play a central role in atherogenesis, and serum markers of inflammation are predictive of cardiovascular disease. Interleukin-2, a pro-inflammatory cytokine produced largely by naive CD4 T cells and Th1 (pro-inflammatory) T cells, has been found in a high proportion of carotid plaques.High-resolution ultrasound of the carotid arteries and serum cytokine levels were measured in stroke-free participants. The mean of the maximum IMT in bilateral bifurcation, common and internal carotid artery segments was measured. Serum levels of interleukin (IL)-1beta, IL-2, IL-6, C-reactive protein, tumor necrosis factor (TNF) alpha and TNF receptors were measured using enzyme-linked immunosorbent assay.IL-2 levels were significantly correlated with IMT (r=0.33, P0.0001), but other cytokines were not. Each unit increase in IL-2 was significantly associated with a mean increase in IMT of 0.18 mm (P=0.0001). After adjusting for other atherosclerotic risk factors, the association was unchanged (mean increase in IMT per unit increase IL-2=0.18 mm, P0.0001). Each standard deviation increase in the level of IL-2 was associated with an increased risk (adjusted odds ratio 1.80, 95% CI 1.12-2.89) for an IMTor =1.0mm (75th percentile for IMT).Serum levels of IL-2, a pro-inflammatory cytokine, are associated with carotid artery IMT, a predictor of stroke and vascular disease. Serum inflammatory markers may provide a novel marker of atherosclerotic risk, and inflammation may provide a new therapeutic target for stroke prevention.

Background: The association between hemostatic activation, stroke mechanism, and outcome is poorly defined. The Hemostatic System Activation Study (HAS) investigators measured serial levels of prothrombin fragment F1.2, a marker of thrombin generation, in patients enrolled in the Warfarin Aspirin Recurrent Stroke Study (WARSS). Methods: HAS enrolled 631 of the 2,206 patients in WARSS. Strokes were subtyped according to inferred mechanism. Plasma was collected for F1.2 at randomization (within 30 days of stroke), 3 months, 12 months, and 18 months. The 3 to 6 month samples in aspirin-treated patients were used for the primary analysis. Results: The authors analyzed 3 to 6 month samples on 320 patients. Higher F1.2 levels were associated with older age, female sex, and hypertension. There was no difference between mean F1.2 levels in 56 cryptogenic (0.9 ± 0.32 nmol/L) and 114 non-cryptogenic (1.13 ± 0.74 nmol/L) patients or across specific stroke subtypes. There was an 8.8%/year ( p = 0.006) increase in mean F1.2 levels. There was a trend toward higher risk of recurrent stroke or death as F1.2 levels increased in aspirin (RR: 1.30, 95% CI: 0.57 to 2.94, p = 0.53) and warfarin treated patients (RR: 1.68, 95% CI: 0.48 to 5.94, p = 0.42). F1.2 levels were reduced on average 70% in warfarin-treated patients in a dose-dependent fashion. Conclusion: F1.2 levels did not appear to differ by stroke subtype, suggesting that factors other than underlying stroke pathophysiology influence thrombin generation in the post-acute stroke period. F1.2 levels were suppressed by warfarin in a dose-dependent fashion. Additional research is needed to determine the predictive value of F1.2 after stroke.

ObjectivesThis study sought to determine the effect of lipoprotein(a), or Lp(a), levels and apolipoprotein(a), or apo(a), sizes on endothelial function and to explore ethnic differences in their effects.BackgroundAlthough high levels of Lp(a) have been shown to confer increased cardiovascular risk in Caucasians, its significance in non-Caucasian populations is uncertain. The pathogenic role of the apo(a) component of Lp(a) is also unclear.MethodsThe relationship of Lp(a) levels and apo(a) sizes to endothelial function was examined in a multiethnic cohort of 89 healthy subjects (age 42 ± 9 years; 50 men, 39 women) free of other cardiac risk factors. Endothelium-dependent, flow-mediated dilation (FMD) and endothelium-independent, nitrate-induced dilation (NTG) were assessed by ultrasound imaging of the brachial artery.ResultsPlasma Lp(a) levels were lowest in Caucasians (18.3 ± 21.1 mg/dl, n = 40); intermediate in Hispanics (30.2 ± 30.5 mg/dl, n = 21); and highest in African Americans (68.8 ± 46.0 mg/dl, n = 28). Lipoprotein(a) levels were found to correlate inversely to FMD (r = −0.33, p < 0.005) but not to NTG (r = 0.06, p = 0.60). This association remained significant after adjusting for gender (p = 0.002). In addition, subjects with small apo(a) size of ≤22 kringle 4 repeats had significantly lower FMD than those with large apo(a) (2.23 ± 2.37% vs. 6.26 ± 4.29%, p < 0.0001), irrespective of Lp(a) levels.ConclusionsThese findings support an independent role of Lp(a) in atherogenesis, an effect that is particularly evident in African Americans. The proatherogenic property of Lp(a) can be attributed in part to its apo(a) component.

Increased left ventricular mass (LVM) and lower socioeconomic status (SES) are predictors of cardiovascular morbidity and mortality. Blacks and Hispanics are more likely to have higher LVM and lower SES. The relation between SES, race–ethnicity, and LVM has not been fully explored. Data were used from the NOMAS population-based sample of 1916 subjects living in Northern Manhattan. SES was characterized on the basis of educational attainment and divided into 4 categories. Echocardiography-defined LVM was indexed according to height at the allometric power of 2.7 and analyzed as a continuous variable. LVM varied by race in our cohort (blacks 48.9 g/m 2.7 , Hispanics 48.4 g/m 2.7 , whites 45.6 g/m 2.7 ; P =0.004). Using ANCOVA, there was a significant inverse and graded association between mean LVM and SES for the total cohort. Mean LVM was 48.4 g/m 2.7 , 48.6 g/m 2.7 , 47.1 g/m 2.7 , and 45.3 g/m 2.7 for the lowest to the highest educational level category ( P trend=0.0004). This relationship remained among normotensives ( P trend=0.0005) and was present for blacks ( P trend=0.009), but not for whites ( P trend=0.86) or Hispanics ( P trend=0.47). The difference in mean LVM between the highest and lowest categories of education was 5.3 g/m 2.7 for blacks, 0.0 g/m 2.7 for whites, and 1.0 g/m 2.7 for Hispanics. Lower SES is an independent predictor of increased LVM among hypertensive and normotensive blacks.

Background and Purpose— The goal of this study was to analyze the association of hemorrhagic presentation with infratentorial brain arteriovenous malformations (AVMs). Methods— The 623 consecutive, prospectively enrolled patients from the Columbia AVM Databank were analyzed in a cross-sectional study. Clinical presentation (diagnostic event) was categorized as intracranial hemorrhage or nonhemorrhagic presentation. From brain imaging and cerebral angiography, AVM location was classified as either infratentorial or supratentorial. Univariate and multivariate statistical models were applied to test the effect of age, sex, AVM size and location, venous drainage pattern, and associated (ie, feeding artery or intranidal) arterial aneurysms on the likelihood of hemorrhage at initial AVM presentation. Results— Of the 623 patients, 72 (12%) had an infratentorial and 551 (88%) had a supratentorial AVM. Intracranial hemorrhage was the presenting symptom in 283 patients (45%), and infratentorial AVM location was significantly more frequent (18%) among patients who bled initially (6%; odds ratio [OR], 3.60; 95% confidence interval [CI], 2.09 to 6.20). This difference remained significant (OR, 1.99; 95% CI, 1.07 to 3.69) in the multivariate logistic regression model controlling for age, sex, AVM size, deep venous drainage, and associated arterial aneurysms. In the same model, the effect of other established determinants for AVM hemorrhage—ie, AVM size (in 1-mm increments; OR, 0.95; 95% CI, 0.94 to 0.96), deep venous drainage (OR, 3.09; 95% CI, 1.87 to 5.12), and associated aneurysms (OR, 2.78; 95% CI, 1.76 to 4.40)—remained significant. Conclusions— Our findings suggest that infratentorial AVM location is independently associated with hemorrhagic AVM presentation.

OBJECTIVE We sought to analyze the perioperative and long-term clinical outcome data for patients with microsurgically treated basilar apex aneurysms. METHODS We identified 98 consecutively treated basilar apex aneurysms in patients prospectively enrolled in a cerebral aneurysm database. RESULTS Fifty patients presented with subarachnoid hemorrhage, and 19 aneurysms were giant. Eighty-four of 98 aneurysms were directly clipped. Surgical morbidity was 19.4% for the entire cohort and 8.8% for the unruptured, nongiant subgroup. The most common complication resulting in long-term morbidity was perforator injury. Sixty-seven percent of patients with clipped aneurysms were independent at discharge; this fraction increased to 79.0% at the 3-month follow-up examination. Good long-term outcomes (modified Rankin Scale score ≤2) were achieved in 56 (70%) of 80 cases. The mean Barthel Index of surviving patients was 95.8 ± 15.0 (median = 100, n = 66). Patients with unruptured, nongiant lesions fared considerably better than patients in other cohorts. Ninety-three percent of this subgroup was independent at discharge; this fraction increased to 100% at the 3-month follow-up examination (n = 27). In univariate analyses, poor clinical grade, giant aneurysm size, major operative complications, and operations performed early in the series were associated with worse outcomes. In the multivariate analysis, unruptured giant aneurysm status was found to confer a tremendous risk for poor outcome (risk ratio, 80.0; 95% confidence interval, 8.0–800.7; P < 0.01). Surviving patients were observed for a mean clinical follow-up period of 7.4 ± 3.7 years. The annual rate of postoperative subarachnoid hemorrhage was 0.18% for all clipped aneurysms and 0% for completely clipped lesions. CONCLUSION In comparison to data from the existing literature regarding Guglielmi detachable coil embolization of basilar apex aneurysms, the data presented suggest that surgical clipping should be an important component of a multimodality approach to the treatment of patients with basilar apex aneurysms.

Background and Purpose— The goal of this work was to determine the effect of age at initial presentation on clinical and morphological characteristics in patients with brain arteriovenous malformation (AVM). Methods— The 542 consecutive patients from the prospective Columbia AVM database (mean±SD age, 34±15 years) were analyzed. Univariate statistical models were used to test the effect of age at initial presentation on clinical (AVM hemorrhage, seizures, headaches, neurological deficit, other/asymptomatic) and morphological (AVM size, venous drainage pattern, AVM brain location, concurrent arterial aneurysms) characteristics. Results— Hemorrhage was the presenting symptom in 46% (n=247); 29% (n=155) presented with seizures, 13% (n=71) with headaches, 7% (n=36) with a neurological deficit, and 6% (n=33) without AVM-related symptoms. Increasing age correlated positively with intracranial hemorrhage ( P =0.001), focal neurological deficits ( P =0.007), infratentorial AVMs ( P P P P =0.001), and lobar ( P P =0.008), and borderzone ( P =0.014) location. No age differences were found for sex, headache, asymptomatic presentation, and venous drainage pattern. Conclusions— Our data suggest a significant interaction of patient age and clinical and morphological AVM features and argue against uniform AVM characteristics across different age classes at initial presentation. In particular, AVM patients diagnosed at a higher age show a higher fraction of AVM hemorrhage and are more likely to harbor additional risk factors such as concurrent arterial aneurysms and small AVM diameter. Longitudinal population-based AVM data are necessary to confirm these findings.

Background and Purpose— Stroke remains a substantial cause of mortality and morbidity in the United States. Racial differences in stroke incidence and mortality persist with well-known excesses among blacks. Information on stroke among Hispanics is limited. In particular, little is known about whether patent foramen ovale (PFO), atrial septal aneurysm (ASA), and other atrial anomalies associated with cryptogenic stroke differ among minority populations. Methods— As a part of the PFO in Cryptogenic Stroke Study, transesophageal echocardiography was performed in a cohort of 630 ischemic stroke patients (mean age, 59±12 years; 44% women; 45% whites, 35% blacks, 17% Hispanics, 3% other). The prevalences of PFO, ASA, and right atrial (RA) anatomy favoring paradoxical embolization were compared among race-ethnic groups. Statistical analyses used analysis of variance for continuous variables and logistic regression for dichotomous variables with adjustments for age and sex. Results— Age- and sex-adjusted prevalences of PFO and ASA were similar across race-ethnic subgroups. However, large PFO was significantly less prevalent among blacks than among whites (odds ratio, 0.47; 95% confidence interval, 0.24 to 0.91; P =0.02). RA anatomy favoring paradoxical embolization was also significantly less prevalent among blacks compared with whites (odds ratio, 0.62; 95% confidence interval, 0.43 to 0.91; P =0.01). There were no significant differences in prevalence between whites and Hispanics. Conclusions— Although the frequency of PFO did not vary among race-ethnic groups, a large PFO and RA anatomy favoring paradoxical embolization were significantly more prevalent among whites and Hispanics compared with blacks. These may be relatively more important risk factors for stroke among whites and Hispanics than among blacks.

There is renewed interest in primate models of acute stroke for the evaluation of potential therapeutic agents prior to clinical trials. The development of more precise functional outcome measures would improve the pre-clinical assessment of neuroprotective strategies. We have constructed a grading scale that utilizes an increased number of goal-oriented tasks to assess both behavior and motor function. The new scoring system is designed to enhance precision and accuracy when compared to existing scales. Twenty-seven male baboons were subjected to 1 h of middle cerebral artery territory occlusion followed by reperfusion. Outcome was evaluated using both a standard neurological function scale and a new task-oriented scale. Each scoring system was assessed for reproducibility (inter-observer reliability) and for association with radiographic infarct volume. The task-oriented grading system was significantly less variable than the standard outcome measure (p0.0001). The task-oriented neurological scale demonstrated stronger correlation with radiographic infarct volume (p0.0001) than the standard scale (p0.01) and more accurately reflected infarct size in animals with small strokes. Compared to the accepted system for grading neurological function, the task-oriented scale demonstrates improved inter-observer variability and a better association with radiographic outcome measures. Incorporating this refined neurological evaluation into a baboon model of stroke may serve to increase the functional predictive value of pre-clinical studies.

BACKGROUND: Using a rat (Lewis-Wistar Furth) abdominal heterotopic transplantation model, we reported previously that the expression of cyclooxygenase (COX)-2 is increased in parallel with that of nitric oxide synthase (NOS)-2 during cardiac allograft rejection. METHODS: To investigate effects of COX-2 inhibition in this model, allograft recipients were treated orally (PO) with 5 mg/kg per day of the tetra substituted furanone selective COX-2 inhibitor 5,5-dimethyl-3-(3 fluorophenyl)-4-(4 methylsulfonal) phenyl-2 (5H)-furanone (DFU) in 1% methyl cellulose solution. RESULTS: In the treated animals, allograft survival was increased from 6.3+/-0.5 to 12.6+/-2.6 days (P = .001). At days 3 and 5 posttransplantation, there were reductions in the extent of the inflammatory infiltrate, endovasculitis, myocardial edema, and cardiomyocyte damage in rejecting allografts. The mean numbers of apoptotic cardiomyocytes determined with the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) technique were significantly reduced in DFU-treated grafts compared with untreated controls (P < 0.05). At day 3 posttransplantation, prostaglandin E2 synthesis by myocardial slices incubated with 100 microM bradykinin was reduced from 1,097+/-156 to 153+/-63 pg/mg of protein in the treated allografts (P < .005). At day 5, COX-2 protein and mRNA together with COX-2, NOS-2, and nitrotyrosine immunostaining in damaged cardiomyocytes were diminished in treated versus control grafts. CONCLUSION: The data indicate that the inhibition of COX-2 prolongs allograft survival and reduces myocardial damage and inflammation during acute cardiac allograft rejection.

Background and Purpose— Leukocyte count has been associated with cardiovascular and cerebrovascular disease, including carotid plaque thickness, in several studies. We hypothesized that white blood cell count is associated with aortic arch plaque thickness (AAPT). Methods— Leukocyte count was measured in randomly selected stroke-free community participants undergoing transesophageal echocardiography. AAPT was measured for each subject and dichotomized into Results— Mean leukocyte count was 5.88±1.76×10 9 /L. Each unit increase in leukocyte count was associated with a mean 0.28-mm increase in AAPT ( P =0.0036). After adjustment for other atherosclerosis risk factors, including age, sex, hypertension, diabetes, hyperlipidemia, and smoking, the relationship persisted (mean increase in AAPT, 0.24 mm; P =0.0064). Thirty-five participants (24.1%) had AAPT ≥4 mm. Mean leukocyte count among those with thick plaque was significantly higher than among those with plaque 9 /L, respectively; P =0.009). Each unit increase in leukocyte count was associated with an increased risk of thick plaque (adjusted odds ratio, 1.38; 95% CI, 1.05 to 1.79). The relationships were similar for men and women and for those Conclusions— Leukocyte count is associated with AAPT and is specifically correlated with AAPT ≥4 mm, a degree of thickening associated with increased stroke risk. These findings are consistent with current hypotheses regarding the inflammatory or infectious etiology of risk of atherosclerosis and stroke.

Background— Nitric oxide synthase-2 (NOS2) is expressed during acute cardiac allograft rejection in association with myocardial inflammation, contractile dysfunction, and death of cardiomyocytes by necrosis and apoptosis. Recently, allosteric inhibitors of NOS2 monomer dimerization that block NOS2 activity have been developed. Methods and Results— To investigate effects of selective NOS2 blockade, 15 mg/kg of BBS-1 or BBS-2 was administered twice daily subcutaneously to rats starting the day of heterotopic heart transplantation. Cardiac allograft survival was increased significantly, from 6.8 days in controls to 13.3 and to 14.2 days in NOS2-inhibited allografts. At day 5 after heart transplantation, synthesis of NOx was reduced by 53%. There were significantly fewer T lymphocytes and macrophages in the inflammatory infiltrate, as well as less edema and cardiomyocyte damage, and the International Society of Heart and Lung Transplantation score fell from 5 to 4 and 3.5. NOS2 and nitrotyrosine immunostaining and the mean numbers of apoptotic cells and of apoptotic cardiomyocytes were significantly diminished in the treated allografts. Conclusions— The data indicate that selective inhibition of NOS2 dimerization prolongs survival and reduces myocardial inflammation and cardiomyocyte damage in acute cardiac allograft rejection.

Object. Proinflammatory adhesion molecule expression has been demonstrated to be elevated in patients with aneurysmal subarachnoid hemorrhage (SAH). Recent studies have shown that elevations in soluble intercellular adhesion molecule—1 (ICAM-1) may be predictive of poor outcome in patients with good grade (Hunt and Hess Grades 1–2) aneurysmal SAH at delayed time points that correspond with the risk period for cerebral vasospasm. In addition, ICAM-1 is upregulated in experimental models of vasospasm. Unfortunately, the relationship of adhesion molecule expression to human vasospasm remains unclear. The authors hypothesized that the delayed elevation of soluble ICAM-1 in patients with aneurysmal SAH is associated with the development of cerebral vasospasm. Methods. Eighty-nine patients with aneurysmal SAH were prospectively enrolled in a study and stratified according to the presence or absence of vasospasm, as evidenced by daily monitoring of transcranial Doppler (TCD) velocities (presence, > 200 cm/second; absence, ≤ 120 cm/second). Levels of soluble ICAM-1 were determined using enzyme-linked immunosorbent assay every other day for 12 days post-SAH. An analysis of covariance model was used to evaluate trends in soluble ICAM-1 levels from 2 days prior to 6 days after the occurrence of documented vasospasm. Two groups of patients, matched for admission admission Hunt and Hess grade, were compared: nine patients with TCD velocities greater than 200 cm/second and nine patients with TCD velocities less than 120 cm/second. From among the patients with TCD velocities greater than 200 cm/second six patients with angiographically documented vasospasm were selected. Patients with TCD velocities less than 120 cm/second and matched admission Hunt and Hess grades but without angiographically documented vasospasm were selected. Patients with TCD-demonstrated vasospasm showed a significant mean rate of rise (p < 0.01) in soluble ICAM-1 levels during the perivasospasm period, but admission Hunt and Hess grade—matched control patients did not (p = not significant [NS]). There was a significant difference between these groups' rates of soluble ICAM increase (p < 0.01). Patients with both TCD- and angiographically demonstrated vasospasm likewise showed a highly significant mean rate of increase in soluble ICAM-1 levels during the perivasospasm period (p < 0.01), whereas admission Hunt and Hess grade—matched controls did not (p = NS). The difference beween these groups' rates of increase was highly significant (p < 0.001). Conclusions. These data suggest a role for ICAM-1 in the pathophysiology of cerebral vasospasm or its ischemic sequelae. As this relationship is further elucidated, adhesion molecules such as ICAM-1 may provide novel therapeutic targets in the prevention of vasospasm or its ischemic consequences.

Objective: To assess the effect of concurrent arterial aneurysms on the risk of incident haemorrhage from brain arteriovenous malformations (AVMs). Methods: In a cross sectional study, 463 consecutive, prospectively enrolled patients from the Columbia AVM Databank were analysed. Concurrent arterial aneurysms on brain angiography were classified as feeding artery aneurysms, intranidal aneurysms, and aneurysms unrelated to blood flow to the AVM. Clinical presentation (diagnostic event) was categorised as intracranial haemorrhage proved by imaging or non-haemorrhagic presentation. Univariate and multivariate statistical models were applied to test the effect of age, sex, AVM size, venous drainage pattern, and the three types of aneurysms on the risk of AVM haemorrhage at initial presentation. Results: Arterial aneurysms were found in 117 (25%) patients with AVM (54 had feeding artery aneurysms, 21 had intranidal aneurysms, 18 had unrelated aneurysms, and 24 had more than one aneurysm type). Intracranial haemorrhage was the presenting symptom in 204 (44%) patients with AVM. In the univariate model, the relative risk for haemorrhagic AVM presentation was 2.28 (95% confidence interval (CI) 1.12 to 4.64) for patients with intranidal aneurysms and 1.88 (95% CI 1.14 to 3.08) for those with feeding artery aneurysms. In the multivariate model an independent effect of feeding artery aneurysms (odds ratio 2.11, 95% CI 1.18 to 3.78) on haemorrhagic AVM presentation was found. No significant effect was seen for intranidal and unrelated aneurysms. The attributable risk of feeding artery aneurysms for incident haemorrhage in patients with AVM was 6% (95% CI 1% to 11%). Conclusions: The findings suggest that feeding artery aneurysms are an independent determinant for increased risk of incident AVM haemorrhage.

The impact of undergoing genetic testing in a Dominican population is not well understood. The objective of this investigation was to evaluate the psychological well-being and perceived cardiac risk among Dominicans who underwent genetic testing. Participants completed a qualitative interview and the Short Form-36 (SF-36) questionnaire after cardiac genetic testing. There were 31 subjects evaluated (mean age 42 ± 11 years). Participants revealed three common themes: (a) fear of dying prematurely, (b) guilt of possibly passing on a mutation to their children, and (c) fear of having an implantable cardioverter defibrillator (ICD) shock. Physical components of the SF-36 were within normal limits (46.2 ± 6.6) but elevated for mental components (59.9 ± 5.3). The quality of life and specific themes results determined in this investigation warrant further research in the Dominican population. El impacto de la experiencia de someterse a pruebas geneticas no esta claramente conceptualizado en la poblacion Dominicana. El objetivo de esta investigacion fue evaluar el bienestar psicologico y los riesgos cardiacos percibidos en los Dominicanos que se sometieron a pruebas geneticas. Los participantes, despues de la realizacion de sus pruebas geneticas cardiacas, completaron una entrevista cualitativa y el cuestionario de calidad de vida SF-36. Treinta y un (31) sujetos fueron evaluados (edad media 42 ± 11 anos). Los participantes revelaron tres temas en comun: (a) el miedo de morir prematuramente, (b) la culpabilidad de trasmitir posiblemente una mutacion genetica a sus ninos y, (c) el miedo de tener un choque del ICD. Los componentes fisicos del SF-36 se encontraban dentro de limites normales (46.2 ± 6.6) sin embargo los componentes mentales se encontraron elevados (59.9 ± 5.3). Los resultados de esta investigacion, calidad de vida y temas especificos, ameritan la realizacion de nuevas investigaciones con la poblacion Dominicana.

Functional health literacy (FHL) has become an increasingly prevalent topic of discussion in patient health and well-being. Although FHL has been studied in a variety of populations, it has not been investigated in patients with pacemakers and implantable cardioverter defibrillators (ICDs).The purpose of this study was to evaluate FHL in a primarily older, urban-dwelling ICD/pacemaker population. A secondary objective was to compare 2 commonly used instruments for assessing FHL.A convenience sample of 116 patients was recruited from an urban ICD/pacemaker clinic. Participants were asked to complete the Short Test of Functional Health Literacy in Adults (STOFHLA) followed by the Test of Functional Health Literacy in Adults to assess reading comprehension and numeracy. Logistic regression was used to assess the association between FHL and patient descriptors.The population was 68 ± 13 years of age, and 62.7% were men. The sample was ethnically diverse: 37.1% white, 39.7% Hispanic, and 22.4% African American; 77.4% of the population reported finishing high school. Of the 109 completing the Test of Functional Health Literacy in Adults, 60.6% had adequate FHL, 10.1% had marginal FHL, and 29.4% had inadequate FHL. The presence of coexisting chronic conditions such as diabetes mellitus, hyperlipidemia, and hypertension was associated with inadequate/marginal FHL (P = .007, P = .004, and P = .02, respectively). Of the 113 completing STOFHLA, 67.3% had adequate FHL, 7.1% had marginal FHL, and 25.7% had inadequate FHL. The presence of diabetes mellitus, hyperlipidemia, and hypertension was also associated with inadequate/marginal FHL as assessed by STOFHLA (P = .009, P = .02, and P = .004, respectively).In this older, urban, ICD/pacemaker population, approximately 40% had inadequate/marginal FHL. These results warrant further investigation of FHL in other cardiovascular populations.

OBJECTIVES The study was done to determine whether coronary steal (defined as an absolute decrease in perfusion from resting blood flow) is induced by intravenous (IV) dipyridamole in patients with severe coronary artery disease (CAD). BACKGROUND Myocardial ischemia during coronary vasodilation is usually attributed to coronary steal. However, there is limited data on the absolute magnitude of coronary steal in humans. METHODS Eighteen patients with multivessel CAD underwent dynamic positron emission tomography (PET) imaging with 13NH3at rest and after infusion of IV dipyridamole. Eight myocardial sectors were analyzed per short axis slice and myocardial blood flow calculated with a two-compartment model in absolute terms. RESULTS Coronary steal occurred in 8 of the 18 patients. In the 8 patients with coronary steal, myocardial blood flow decreased from 90 ± 18 ml/100 g/min at rest to 68 ± 27 ml/100 g/min following dipyridamole in the segments with steal, and increased from 87 ± 19 to 138 ± 16 ml/100 g/min following dipyridamole in the segments without steal. Significant clinical correlates of coronary steal were either ST elevation or the combination of ST depression and angina. CONCLUSIONS Coronary vasodilation with IV dipyridamole is associated with significant reductions in blood flow to collateral-dependent myocardium consistent with coronary steal in about 45% of patients with severe CAD.

Background —Inflammation may be involved in the origin of transplant coronary artery disease. We hypothesized that plasma levels of C-reactive protein (CRP) and interleukin-6 (IL-6), markers for systemic inflammation, would correlate with cardiac transplant graft survival. Methods and Results —We studied 99 consecutive cardiac transplant recipients who were referred for routine endomyocardial biopsy and/or surveillance coronary angiography. Plasma levels of CRP and IL-6 were measured by their respective ELISAs. Patients were divided into 2 groups: those who died or required retransplantation and those who survived without the need for retransplantation. During the follow-up period of 5.0±2.7 years (range, 0.2 to 15.1 years) after transplant, 20 patients died and 9 required retransplantation. There was no significant difference in age, race, sex, cause of native myopathy, presence of diabetes, or use of aspirin, statins, or calcium channel blockers between the 2 groups. Although IL-6 did not relate to graft failure, CRP level was predictive of allograft failure ( P =0.003). The risk of allograft failure increased 36% for every 2-fold increase in CRP level. Moreover, CRP levels also correlated significantly with the frequency of grade 3 rejection ( P =0.02). In multivariate analysis, when combined with other significant predictors such as donor age and sex mismatching of the graft, CRP still significantly predicted graft failure ( P =0.025) with a 32% increase in the risk of graft failure for every 2-fold increase in CRP level. Conclusions —These findings suggest that elevated plasma levels of CRP are associated with subsequent allograft failure in cardiac transplant recipients.

Abstract —Asymmetric dimethylarginine (ADMA), a compound detectable in human plasma, is an endogenous inhibitor of NO synthase. Endothelial dysfunction is an early event in atherogenesis, and large-vessel atherosclerosis is a major cause of morbidity and mortality in patients with type 2 diabetes mellitus. Fifty patients with type 2 diabetes mellitus were studied at baseline and 5 hours after ingestion of a high-fat meal. Plasma ADMA measured by using high-performance liquid chromatography increased from 1.04±0.99 to 2.51±2.27 μmol/L ( P P

Background —The hypothesis that cyclooxygenase-2 (COX-2) is involved in the myocardial inflammatory response during cardiac allograft rejection was investigated using a rat heterotopic abdominal cardiac transplantation model. Methods and Results —COX-2 mRNA and protein in the myocardium of rejecting cardiac allografts were significantly elevated 3 to 5 days after transplantation compared with syngeneic controls (n=3, P l -lysine. At posttransplant day 5, inhibitor administration resulted in a significant reduction of COX-2 mRNA expression (3764±337 versus 5110±141 arbitrary units, n=3, P P P Conclusions —The data indicates that COX-2 expression is enhanced in parallel with iNOS in the myocardium during cardiac allograft rejection.

Background and Purpose —Aortic arch atheromas (AAs) have been shown to be a risk factor for ischemic stroke (IS) in the elderly because of their potential for cerebral embolization. However, the association between AAs and the presence of cerebral microemboli has not been clearly established. The aim of this study was to determine whether large AAs are associated with an increased frequency of high-intensity transient signals (HITS) in elderly patients with IS. Methods —We performed bitemporal simultaneous HITS monitoring of both middle cerebral arteries in 62 consecutive elderly patients with acute IS (mean age 72.5±8.8 years, 65% men). In 16 patients, one or both temporal windows were inadequate; therefore, the analysis of HITS was performed in the remaining 46 patients. All patients underwent omniplane transesophageal echocardiography (TEE), and they had no significant extracranial or intracranial artery disease and no cardiac prosthetic valves. Large AA was defined as ≥4 mm in thickness. Complex AA was defined as ulcerated or mobile, regardless of plaque thickness. HITS monitoring was performed within 24 hours of TEE and analyzed by an experienced neurologist-sonographer blinded to TEE findings. A 9-dB threshold was chosen to discriminate HITS from background Doppler signal. The HITS counts in the left and in the right middle cerebral arteries were added and reported as a total number of HITS in 30 minutes. Results —HITS were detected in 14 (78%) of 18 patients with large AAs versus 8 (29%) of 28 patients with no or small AAs (odds ratio [OR] 8.8, 95% CI 2.2 to 34.8; P =0.001). The association was also present in 27 patients with no other cardiac embolic sources, such as atrial fibrillation, patent foramen ovale, spontaneous echo contrast, and thrombus (7 of 10 patients with large AAs versus 3 of 17 patients with small or no AA; OR 10.9, 95% CI 1.7 to 68.5; P =0.013). Complex AAs were associated with a higher frequency of HITS than were noncomplex AAs (6 of 6 patients with complex AAs versus 15 of 39 patients with noncomplex AAs; OR 2.6, 95% CI 1.7 to 3.9; P =0.005). Conclusions —HITS are significantly associated with large AAs in elderly stroke patients. This observation may support the causal role of large AAs in IS.

Background and Purpose —The association between left atrial size and ischemic stroke is controversial and has been suggested to exist only in men and to be mediated by left ventricular mass. Data are available almost exclusively for white patients. The purpose of this study was to evaluate the association between left atrial size and ischemic stroke in a multiethnic population. Methods —A population-based case-control study was conducted in 352 patients aged >39 years with first ischemic stroke and in 369 age-, gender-, and race-ethnicity–matched community controls. Left atrial diameter was measured by 2-dimensional transthoracic echocardiography and indexed by body surface area. Conditional logistic regression analysis was performed to assess the risk of stroke associated with left atrial index in the overall group and in the age, gender, and race-ethnic strata after adjustment for the presence of other stroke risk factors. Results —Left atrial index was associated with ischemic stroke in the overall group (adjusted OR 1.47 per 10 mm/1.7 m 2 of body surface area; 95% CI 1.03 to 2.11). The association was present in men (adjusted OR 2.81, 95% CI 1.42 to 5.57) but not in women (adjusted OR 1.08, 95% CI 0.70 to 1.66), and in patients aged 60 years (adjusted OR 1.23, 95% CI 0.84 to 1.81). Subgroup analyses showed the risk to be present in men across all age subgroups. In women, the lack of association between left atrial index and stroke was most strongly influenced by left ventricular hypertrophy. A trend toward an association between left atrial index and stroke was observed in whites (adjusted OR 1.81, 95% CI 0.81 to 4.09) and Hispanics (adjusted OR 1.61, 95% CI 0.98 to 2.65) but was less evident in blacks (adjusted OR 1.25, 95% CI 0.74 to 2.14). Conclusions —Left atrial enlargement is associated with an increased risk of ischemic stroke after adjustment for other stroke risk factors, including left ventricular hypertrophy. The association is observed in men of all ages, whereas in women it is attenuated by other factors, especially left ventricular hypertrophy. Interracial differences in the stroke risk may exist that need further investigation.

Background —The de novo occurrence of sustained ventricular tachycardia (VT) after CABG has been described, but the incidence, mortality rate, long-term follow-up, and mechanism are not well defined. Methods and Results —This prospective study enrolled consecutive patients undergoing CABG at a single institution. Patients were followed up for the development of sustained VT, and a detailed analysis of clinical, angiographic, and surgical variables associated with the occurrence of VT was performed. A total of 382 patients participated, and 12 patients (3.1%) experienced ≥1 episode of sustained VT 4.1±4.8 days after CABG. In 11 of 12 patients, no postoperative complication explained the VT; 1 patient had a perioperative myocardial infarction. The in-hospital mortality rate was 25%. Patients with VT were more likely to have prior myocardial infarction (92% versus 50%, P P P P P P Conclusions —The first presentation of sustained monomorphic VT in the recovery period after CABG is uncommon, but the incidence is high in specific clinical subsets. Placement of a bypass graft across a noncollateralized total occlusion in a vessel supplying an infarct zone was strongly and independently associated with the development of VT.

We tested the hypothesis that an increased body mass index was similarly associated with impaired endothelial function as measured by flow-mediated dilation in a high-risk, Hispanic population of men and women living in northern Manhattan. The association of flow-mediated dilation and body mass index was significant in women (beta -0.16 +/- 0.04, p0.0001) but not in men (beta -0.02 +/- 0.06, p = 0.72). This is the first study to demonstrate a gender-specific difference in endothelial function associated with body mass index.

Background and Purpose Patent foramen ovale (PFO) is associated with stroke of unknown etiology or cryptogenic stroke. However, optimal treatment to prevent recurrence in cryptogenic stroke patients with PFO is not clearly defined. Since PFO represents a surgically repairable lesion, interest in closing it is high. This report reviews our experience with cryptogenic stroke patients with PFO who underwent surgical PFO closure and were followed for recurrence of neurological events. Methods We followed 28 cryptogenic stroke patients (17 men, 11 women; mean age, 41±13 years) with transesophageal echocardiograpy–defined PFO who had undergone PFO closure by open thoracatomy. All patients selected for surgery refused, could not take, or failed warfarin therapy. They were followed by physician visits and telephone interviews. Results There were no surgical complications. With a mean follow-up of 19 months, four patients experienced neurological event recurrence, one stroke, and three transient ischemic attacks. Kaplan-Meier survival analysis demonstrated that the actuarial rate of recurrence was 19.5% (95% confidence limit 2.2-36.8%) at 13 months of follow-up. None of the 17 patients (0%) younger than 45 years suffered a recurrence, whereas four of 11 patients (35%) aged 45 or older experienced a recurrence of neurological event ( P Conclusions Although PFO is easily repairable in patients with cryptogenic stroke, its closure does not consistently prevent recurrence of ischemic events. The recurrence appears to occur more frequently in older cryptogenic stroke patients.

Background and Purpose Valvular strands, thin filamentous material attached to the mitral or aortic valve, are seen during transesophageal echocardiography and have been associated with stroke. Little is known about this association in different age, sex, and race-ethnic subgroups and the effect of various strand characteristics on this association. Methods From patients referred for transesophageal echocardiography, 73 patients with recent ischemic stroke (68) or transient ischemic attack (5) were age matched to 73 stroke- and transient ischemic attack–free control subjects. The association between valvular strands and cerebral ischemia was evaluated for the overall group and demographic subgroups. The effect of strand location, length, number, and valve thickness was also determined. Results An association between cerebral ischemia and valvular strands was observed (odds ratio [OR]=4.4; 95% confidence interval [CI]=2.0 to 9.6). The association was found for both men and women and among all three race-ethnic groups. The OR was greater in those who were younger (12.5 [95% CI=2.4 to 64.5] for age Conclusions Valvular strands, whether mitral or aortic, are associated with ischemic stroke, especially among younger persons.

Summary Background A small proportion of strokes are caused by cerebral arteriovenous malformations (AVM). Treatment to prevent intracranial haemorrhage itself carries risks, and untreated AVM may in many cases have a good prognosis. We investigated the risk of subsequent symptomatic bleeding in the clinical course of AVM in patients with and without an initial haemorrhage. Methods 281 unselected, consecutive, prospectively enrolled patients with cerebral AVM were grouped according to their initial clinical presentation—142 presented with and 139 without haemorrhage. The frequency of AVM haemorrhages during the subsequent clinical course (before the start of endovascular, surgical, or radiation treatment) in the two groups was compared by means of Kaplan-Meier life-tables, log-rank test, and multivariate proportional-hazards regression models. Haemorrhage was defined as a clinically symptomatic event with signs of acute bleeding on computed tomography or magnetic resonance brain imaging. Findings During mean follow-up of 8·5 months for the haemorrhage group and 11·9 months for the non-haemorrhage group, haemorrhages occurred in 18 (13%) of the former patients and in three (2%) of the latter (p=0·0002). The annual risk of haemorrhage was 17·8% and 2·2%, respectively. In the multivariate regression model, the adjusted hazard ratio for haemorrhage at initial presentation was 13·9 (95% Cl 2·6–73·8; p=0·002). Deep venous drainage (hazard ratio 4·1 [1·2–14·9], p=0·029) and male sex (9·2 [2·1–41·3], p=0·004) were also significantly associated with subsequent haemorrhage, but no significant association was found for age or AVM size. The annual rate of spontaneous haemorrhage was 32·6% for men and 10·4% for women in the haemorrhage group compared with 3·3% for men and 1·3% for women in the non-haemorrhage group. Among patients with haemorrhage at initial presentation, the risk of haemorrhage fell from 32·9% in year 1 to 11·3% in subsequent years (34·2% to 31·0% in men; 31·1% to 5·5% in women). Interpretation In AVM, patients initially presenting with haemorrhage have a higher risk of subsequent bleeding than those presenting with other symptoms. The risk is higher in men than in women.

Background and Purpose— We evaluated the association between electrocardiographic left atrial abnormality (ECG-LAA) and ischemic stroke, especially whether ECG-LAA provides additional prognostic information to that provided by echocardiography. Methods— A population-based, case-control study included 146 patients with first ischemic stroke and 195 age-, gender-, and race/ethnicity-matched community control subjects. ECG-LAA was defined as either P-wave duration >120 ms or P-terminal force in precordial lead V 1 (PTFV 1 ) >40 ms·mm. Results— PTFV 1 >40 ms·mm was associated with ischemic stroke after adjustment for other stroke risk factors (odds ratio [OR], 2.32; 95% CI, 1.29 to 4.18). The association remained significant after adding echocardiographic left atrial diameter to the model (OR, 2.31; 95% CI, 1.28 to 4.17). PTFV 1 was independently associated with stroke in patients in the upper half of echocardiographically determined left ventricular mass (adjusted OR, 4.5; 95% CI, 2.20 to 9.15) but not in those in the lower half (OR, 0.58; 95% CI, 0.20 to 1.65; P =0.0008). Conclusions— ECG-LAA can supplement 2D echocardiography in assessing the risk of ischemic stroke, especially in subjects with increased left ventricular mass.

To assess the effects of positive cardiac genetic diagnoses, ICD discharges, and arrhythmias on measures of psychological well-being.Fifty-eight adults with prior cardiac genetic testing were enrolled. Patient well-being was determined using the SF-36 (QoL), HADS-A and HADS-D (anxiety/depression), and IPQ-R (patients' perceptions of illness). Patients with positive and negative cardiac genetic test results were compared using non-parametric statistics.Genetic testing yielded 76% with a positive diagnosis and 29% reported an ICD shock. QoL assessments (n = 33) were within normal ranges (mean of 50) with the exceptions of general health (44.1 ± 12.2, p 0.01) and bodily pain (55.1 ± 9.1, p 0.01) domains, but only the bodily pain domain showed differences between those with positive and negative cardiac genetic test results. Subjects with ICD discharges had higher scores than those without shocks in consequential and emotional IPQR subscales as well as greater perceived risks of experiencing a serious cardiac event, developing additional symptoms, or limitations in daily activities.Positive genetic results did not negatively impact patient well-being with the exception of the bodily pain domain of the SF-36.

Background Apoptosis is a distinct form of programmed cell death characterized by activation of endonucleases that cleave nuclear DNA, condensation and fragmentation of nuclear chromatin, blebbing of intact membranes, and cell shrinkage and fragmentation. The mechanisms responsible are unclear, but nitric oxide (NO) generated by inducible NO synthase (iNOS) has been demonstrated to induce apoptosis in macrophages in vitro. This study investigated whether apoptosis occurs during cardiac allograft rejection and examined the relationship of apoptosis to iNOS expression. Methods and Results Heterotopic abdominal transplantation from Lewis to Wistar-Furth rats was used as a model of cardiac allograft rejection; Lewis-to-Lewis grafts served as controls. Apoptosis was identified by DNA ladders after electrophoresis on agarose gels and by in situ labeling of DNA fragments; cell types were determined by immunohistochemistry. The number of apoptotic cardiac myocytes increased sharply from day 3 (0.31/mm 2 ventricular tissue) to day 5 (1.27/mm 2 ) after transplantation. At day 5, allografts showed a significant increase ( P Conclusions Apoptosis of myocardial cells occurs during cardiac allograft rejection. Apoptosis during rejection parallels the expression of iNOS, which suggests that apoptosis may be triggered by NO and peroxynitrite.

Background To evaluate factors that explain sex differences affecting mortality after cardiac transplantation, a retrospective analysis of adult patients undergoing orthotopic cardiac transplantation was undertaken at the Columbia-Presbyterian Medical Center. Methods and Results The study population consisted of 379 patients (75 women, 304 men) ≥18 years of age who survived for ≥48 hours after undergoing orthotopic cardiac transplantation between March 1985 and March 1992. The following were analyzed: incidence of death and treated rejection episodes, donor and recipient cytomegalovirus (CMV) matches, use of OKT3 induction therapy, and donor and recipient HLA mismatches. Women 49±12 years old and men 47±12 years old were characterized by differences in race and diagnosis. Women were more likely to be nonwhite ( P P P =.08). Overall actuarial survival was significantly reduced in women after transplantation ( P P P P Conclusions (1) Women are at risk for reduced actuarial survival up to 3 years after cardiac transplantation. (2) Univariate analysis shows that women are selectively at risk for death when receiving hearts from CMV(+) donors and after receiving OKT3 induction therapy. (3) Multivariate analysis reveals that women are at even greater risk for death when receiving hearts from CMV(+) donors in conjunction with OKT3 induction therapy. (4) In the absence of OKT3 use, the greatest risk of death occurs in CMV(−) women transplanted with CMV(+) donor hearts. (5) When female to male survival curves are compared, factors that influenced survival in women did not appear to be problematic in men.

The purpose of this study was to describe the clinical, research, educational, and professional activities that nurses are engaged in following participation in a 2 month intramural genetics training program. An online survey was administered in 2010 to graduates of the program sponsored by the US National Institute of Nursing Research from 2000 to 2009, in Bethesda, Maryland, USA. The electronic, voluntary survey was sent to 189 graduates via email. The survey included demographic characteristics, educational preparation, professional roles and responsibilities, and attitudes about genetic testing and privacy issues. Of the 95 graduates responding to the survey, 74% had doctorates and 70% were advanced practice nurses. All respondents reported incorporating genetics knowledge into daily clinical, academic, or research practices since completing the program, with 72% reporting being involved in genetically-focused research (52% with research funding), 32% incorporating genetics into patient care, and 79% providing genetics education. Respondents working in a hospital setting or academic institution were more likely to desire additional training in genetics. National Institute of Nursing Research graduates have successfully integrated genomics into a variety of nursing practices.