bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 81: Hemogenic Endocardium Contributes to Cardiac Tissue Macrophages
Authors: Shigeta Ayako , Huang Vincent , Zuo Jonathan , Shou Bin , Nakano Haruko , Nakano Atsushi
Published: July 2021

Transient phase of hematopoiesis in mammalian embryo occur in multiple anatomical sites including yolk-sac, placenta and the aorta-gonad-mesonephros region. A recent report demonstrates that endocardium also contribute to definitive hematopoiesis during embryogenesis. CD41+ hemogenic endocardial cells are enriched in the endocardial cushion in the outflow tract and atrial-ventricular canal at around embryonic day 9.5-11.5. Here we show the hemogenic endocardium as a novel source of cardiac tissue macrophages (cTMs). The fate of endocardial cells were traced using nuclear factor of activated T-cells 1 (Nfatc1)-cre mouse line, a Cre driver specific to the endocardium. Flow-cytometry study using

NFATc1
cre/+
; R26YFP
reporter/+

with CD45, CD11b and F4/80 demonstrated that endocardially-derived cardiac tissue macrophages (EcTMs) were found in the heart from embryonic day 10.5 to adult stages. The number of EcTMs gradually expanded from embryonic day 15.5 to postnatal 8 and were maintained until adult stage. Immunofluorescent staining with CD68, F4/80 and CD206 revealed that EcTMs were identified in the cardiac cushion at embryonic day 13.5 and 15.5, and persisted in the valve mesenchyme and atria after birth. To assess their functional potential, we characterized their M1/M2 polarity. Surface marker analyses indicate that EcTMs in embryo were classified exclusively as M2 type whereas non-endocardially-derived cTMs (non-EcTMs) contributed to both M1 and M2 type. EcTMs in postnatal hearts were also predominantly M2 type. Genome-wide transcriptome analysis showed that genes related to antigen presenting and phagocytosis were significantly more upregulated in EcTMs compared to non-EcTMs. These findings indicate that the hemogenic endocardium contributes to M2-type cTMs in endocardial cushion and valve mesenchyme throughout embryogenesis and postnatal heart. Cardiac tissue macrophages migrate to the heart in multiple waves including postnatal bone marrow, fetal liver during embryonic stages, and possibly yolk sac prior to the liver colonization. Our results suggest that the 4
th
population of macrophages originate directly from the local hemogenic endocardium.
Abstract 86: Mapping and Inducing Ventricular Tachycardia in Cardiomyopathic Animal Models
Authors: Chinyere Ike , Weigand Kyle , Moukabary Talal , Witte Russell , Chu Miensheng , Novak Stefanie , Hutchinson Mathew , Lancaster Jordan , Gregorio Carol , Goldman Steven , Juneman Elizabeth
Published: July 2021

Introduction:
In the United States, one in three deaths is attributed to cardiovascular disease (CVD). With CVD, sudden cardiac death is a common cause of mortality, specifically by way of ventricular tachycardia (VT) and ventricular fibrillation. We propose the application of our custom software to evaluate the electrophysiologic (EP) properties of animal models of ischemic and non-ischemic dilated cardiomyopathies.

Methods:
Adult male Sprague-Dawley rats with left coronary artery ligation and adult male and female transgenic Fragile X cardiomyopathic mice were sedated with Inactin and Isoflurane, respectively, and underwent hemodynamic measurements and/or EP testing. Using a PowerLab system and LabChart software, three-lead electrocardiograms were recorded. Using a pressure catheter, hemodynamic parameters were calculated. Using a concentric microelectrode (World Precision Inc.), a clinical EP catheter (Bard Inc.), and custom MATLAB software, local epicardial monophasic action potentials (MAP) and local epicardial voltages were recorded. Using custom MATLAB software for programmed electrical stimulation (PES), VT was induced epicardially with a clinically-accepted drivetrain. Animals underwent eight equidistant ‘S1’ stimulations followed by a premature ‘S2’ stimulation. The S2 stimulation was decreased by 5 milliseconds until loss of capture, indicating the effective refractory period. Sustained ventricular tachycardia (sVT) has been defined as more than fifteen consecutive premature ventricular contractions.

Results:
The chronic heart failure (CHF) rats had documented hemodynamic heart failure with elevated LV EDPs, and decreased EFs. Mapping and PES was performed on the two groups of rats, namely CHF and Sham-operated. In the CHF group, 71% (27/39) of the rats exhibited sVT, while 0% (0/10) of the Sham-operated rats exhibited sVT. Mapping was also performed on the two groups of mice, namely Wild-Type and Fragile X.

Conclusions:
We have performed clinically-relevant EP studies in CHF rats and in Fragile X dilated cardiomyopathic mice. These EP studies demonstrate our ability to evaluate and validate the phenotypes of animal models of cardiomyopathies and demonstrate the potential to evaluate the effectiveness of new therapies.
Abstract 98a: A Novel Rodent Model of HFpEF: a Potential Platform for Understanding Disease Mechanisms and Evaluating New Therapies
Authors: Zhao Huawei , Campbell Barry R , Shen Xiaolan , Madwed Jeffrey B , Hoek Maarten
Published: July 2021

Heart failure with preserved ejection fraction (HFpEF) occurs in over 50% of total HF population today and is growing with no approved therapies today. A major challenge to the field is that truly representative experimental models of HFpEF do not exist and therefore, the advancement of the science and treatment is minimal. We have set out to develop a reliable and reproducible HFpEF rodent model to provide a platform for preclinical investigation of potential therapies. Diagnostic criteria to validate the model included (a) LVEDP > 15 mmHg, (b) left ventricular (LV) stiffness and impaired LV relaxation, (c) preserved ejection fraction (EF ≥ 55%), and (d) LV concentric hypertrophy. Adult SHR were given isoproterenol by subcutaneous mini pump infusion for 4-weeks. After first week of isoproterenol treatment initiated, L-NAME was added for 8-weeks to accelerate transition from concentric hypertrophy to HFpEF. Echocardiography and invasive hemodynamics were used to evaluate cardiac structure and function at baseline, immediately after stopping L-NAME and at 4 and 8 weeks. Treated SHR had significantly increased LVEDP, Tau and left ventricular hypertrophy with preserved EF. A follow-up study confirmed these initial data and demonstrated this HFpEF phenotype remained for at least 8-week after end of L-NAME/Iso treatment (see table). This rodent model mimics many characteristics of HFpEF patients, such as concentric cardiac hypertrophy, slow LV relaxation, and increased LV stiffness with a chronic hypertensive background and may provide a valuable platform for understanding the pathophysiology of HFpEF, as well as facilitating preclinical investigation of potential therapies.
Function of the Chronically Diseased Kidney
Authors: GOTTSCHALK CARL W.
Published: July 2021

Adaptive morphological and functional changes in the chronically diseased kidney are described in historical perspective and their correlation is stressed. The consequences of decreased glomerular filtration rate (GFR) in the presence of unchanged dietary intake on the mechanisms of excretion of substances passively reabsorbed, actively reabsorbed, and secreted are reviewed. Under these circumstances the plasma concentrations of creatinine and urea are necessarily elevated, but not that of electrolytes with regulated tubular transport. In the case of sodium, fractional excretion and GFR are reciprocally related in order to maintain unchanged rates of excretion and plasma concentration. With phosphate, regulated tubular reabsorption can prevent an increase in plasma concentration provided the GFR does not fall below approximately 25 ml/min. In the case of potassium, tubular secretion becomes apparent at marked decreases in filtration rate.

These adaptive regulatory changes are considered predictable and necessary in order for the patient to survive, and are supported by compensatory morphological changes in some of the surviving nephrons. Heterogeneity in size of the surviving nephrons, particularly the proximal tubules and glomeruli, is documented and the prediction is made that these structural changes are associated with appropriate changes in rates of transport. Data are presented demonstrating marked heterogeneity of nephron filtration rates and proximal tubular transit times in experimentally diseased kidneys. The necessity of utilizing appropriate methods of study to obtain data on individual nephrons is stressed, as is the lack of knowledge concerning the mechanisms that lead to the compensatory structural and functional changes.

It is concluded that the adaptive changes exhibited by the kidney with chronic renal disease are another and a special example of adaptive growth and, therefore, that it is more appropriate to think in terms of "adaptive nephrons" and not "intact nephrons".
Further Studies of a Natriuretic Substance Occurring in Human Urine and Plasma
Authors: SEALEY JEAN E. , LARAGH JOHN H.
Published: July 2021

Studies are presented which provide additional physiological and biochemical characterization of a natriuretic agent which has been identified in extracts of plasma and urine of human subjects. The natriuretic activity of active fractions was consistently demonstrable in normal hydropenic rats as well as in rats with congenital diabetes insipidus. The induced natriuresis usually developed slowly and could last for several hours. The natriuresis was not usually associated with increases in water or potassium excretion. It occurred without measurable changes in glomerular filtration rate or arterial blood pressure. Altogether, these results suggest that the substance acts to depress sodium reabsorption in the distal tubule.

In bioassays of similarly prepared fractions utilizing direct perfusion of the renal artery, an immediate and transient natriuresis has been consistently observed. This immediate response appears to be produced by a substance different from that responsible for the delayed and more prolonged natriuresis, because the immediate response was always associated with a rise in blood pressure in the assay animal. Also, the activity of the agent responsible for the immediate natriuresis did not fluctuate with changes in sodium balance in the experimental subjects. Contamination with this substance may explain the occasional immediate response observed in earlier assays. This experience points to the importance of monitoring blood pressure during assays for natriuretic agents.

Additional fractionation studies continue to suggest that the substance occurring in salt-loaded human subjects which causes the more delayed and prolonged natriuresis in assay animals appears to be of a molecular weight of from 10,000 to 50,000.
Task Difficulty, Depression, and Life Changes in Family Caregivers of Stroke Survivors
Authors: Bakas Tamilyn , Williams Linda S , Chadwick Linda , Jessup Samantha L
Published: July 2021

15

Background/Purpose:
Over 39% of stroke caregivers suffer from depression. Little is known about the specific caregiving tasks that are associated with depression or the life changes that stroke caregivers experience while providing care. The purpose of this study is to describe the relationships between task difficulty, depression, and life changes in family caregivers of stroke survivors.
Methods:
As part of a larger study of quality of life in stroke survivors, 32 family caregivers self-completed questionnaires containing the Caregiving Burden Scale (CBS), Center for Epidemiological Studies Depression Scale (CES-D), and the Bakas Caregiving Outcomes Scale (BCOS) with alpha reliabilities ranging from .74 to .96. Relationships between variables were analyzed with Pearson r. A majority of the caregivers were female (94%), with 69% spouses and 31% adult children. African Americans comprised 10% of the sample with 87% Caucasians and 3% from other ethnic backgrounds. A majority of the caregivers were providing care 1 to 6 months following the stroke (97%).
Results:
Preliminary results indicate that depression and task difficulty were strongly correlated (r = .67, p<.001), as were depression and negative life changes (r = .72, p<.001). Task difficulty and negative life changes were also strongly correlated (r = .72, p<.001). Based on comparison of CBS item means, the most difficult tasks for caregivers were behavioral management (moodiness, irritability, confusion, memory loss, etc.) and providing emotional support. Based on comparison of the BCOS item means, the most negative life changes were decreased time for family and friends.
Conclusions:
These preliminary results suggest the need for intervention development in the areas of behavioral management, emotional support, and respite for family caregivers of stroke survivors. Educating family caregivers about effective communication strategies and cognitive behavioral techniques to use in dealing with the stroke survivor are potential areas for future study. Because data collection is still in progress, findings from a larger sample will be presented.
Stroke hospitalization and case-fatality in the United States, 1988–1997
Authors: Fang Jing , Cohen Hillel , Alderman Michael H
Published: July 2021

23

Age-adjusted stroke mortality in the US has declined in recent decades. However, little is known about stroke morbidity. Using the National Hospital Discharge Survey data from 1988 to 1997, we examined the change in stroke hospitalization and case-fatality in the US. During the 10 years, age-adjusted stroke hospitalization rate increased 22% (from 381 to 463/100,000, p=0.048). By regions, stroke hospitalization rates overall were 641, 600, 562 and 438 for the South, Midwest, Northeast, and West respectively (p<0.05), and were increased in all regions during the 10 years. Overall, 58% of stroke hospitalizations were due to ischemic stroke, 13% due to hemorrhagic stroke, and 29% were classified as other stroke. The hospitalization rates were 74.8 and 332.4 per 100,000 respectively for hemorrhagic and ischemic strokes and the increase rate in 10 years were 13.5% (p=0.214) and 31.5% (p=0.044) respectively. During 10 years, stroke patients with diabetes, hypertension and congestive heart failure increased 17.4% (p=0.17), 34% (p=0.05), and 31% (p=0.091) respectively. The average length of hospital stay reduced from 11.1 to 6.2 days (decrease of 44.1%), with an average annual percentage decrease of 6.1% (p=0.012). Although the total number of patients hospitalized for stroke increased during this period, the total person-days in hospital decreased 22% (p=006). In-hospital death among stroke decreased steadily from 12.7% to 7.6% (decrease of 40%, p=0.04). In-hospital case-fatality was estimated by stratifying patients on age, gender, region, type of stroke, and other co-morbidity. Case-fatality rate was substantially higher among patients with hemorrhagic than ischemic stroke (28.0% vs 5.8%, p<0.01); among patients with congestive heart failure than those without (17.9% vs 8.5%). In addition, patients of old age (≥75 years), men, those living in the Northeast had higher case-fatality rates than those younger, women and living in elsewhere. In conclusion, the declining of age-adjusted stroke mortality in the US has not been found to be related to the decrease in incidence. However, the observed reduction in hospital case-fatality might contribute to the decline of stroke mortality.
Carotid Endarterectomy In Octogenarians: Is It Worth The Effort?
Authors: Ascher Enrico , Gade Prasad , Hingorani Anil , Gunduz Yilmaz
Published: July 2021

96

Objective.
Safety, effectiveness and cost issues of carotid endarterectomy (CEA) in the elderly patient have been debated because of limited life expectancy and presumably increased complications. We compared characteristics of two populations who underwent CEA: 80 or older (older group) and 65–79 year old patients (younger group).
Methods.
Medical and financial data were obtained by retrospective review of hospital charts and billing records. Recent follow-up was accomplished by telephone interview. Life-table and Chi-square tests were used for statistical analysis. We analyzed 109 CEAs performed in 101 older patients from 2/1/90 to 8/30/97 and 125 CEAs performed in 121 younger patients.
Results.
Comparing the older with younger groups, there were no differences in gender (50% male vs 59%), incidence of preop CVA (22% vs 17%) history of TIA (23% vs 25%), amaurosis fugax (6% vs 8%), hypertension (62% vs 60%), combined perioperative death and stroke rate (1.8% vs 1.7%) or other complications (11% vs 10%). Significant differences (p<0.05) were noted between older and younger groups in incidence of diabetes (17% in the older group vs 30%) , smoking (39% vs57%) and heart disease (48% vs 28%). Length of stay (2.8 in older group vs 3.0 days) or hospital cost including readmission for treatment of complications ($9,400 in older vs $7,842) were similar. Survival rates were not significantly different at the end of three years of follow up.
Conclusions.
Carotid endarterectomy can be performed in the elderly as safely and cost effectively as in the younger population.
MULTIFREQUENCY DOPPLER DISCRIMINATES BETWEEN GASEOUS AND SOLID MICROEMBOLI
Authors: Professor David Russell , Professor Rainer Brucher
Published: July 2021

110

Introduction:
Although cerebral microemboli may be detected using transcranial Doppler, it is at present extremely difficult to determine if they are composed of gaseous or solid elements. Theoretically this is possible by insonating an embolus simultaneously with two different ultrasound frequencies since the reflected ultrasound power will differ for each frequency depending on embolus type.
Methods:
The Doppler instrumentation used in this study discriminates between solid and gaseous microemboli by insonating them simultaneously with 2.0 and 2.5 MHz frequencies. In the experimental part of the study 61 solid (50–80 μm plastic) and 45 gaseous (15–30 μm) microemboli were introduced into a pulsatile closed-loop system. Five prosthetic heart valve patients and 10 carotid artery stenosis patients took part in the clinical studies. Results : In the experimental study analysis of the reflected Doppler power for the two different ultrasound frequencies showed correct differentiation between solid (N = 61) and gaseous (N = 45) microemboli for 95% of the microembolic events. Four hundred microemboli in the 5 prosthetic heart valve patients and 20 microemboli in the 10 carotid stenosis patients were analysed. In the prosthetic heart valve patients 344 (86%) were gaseous and 56 (14%) solid whereas all 20 (100%) microemboli in the carotid stenosis patients were solid.
Conclusions:
These studies have shown that it is now possible to discriminate between solid and gaseous cerebral microemboli using multifrequency transcranial Doppler monitoring.
Clinically Meaningful MRI Perfusion Abnormalities in Acute Stroke: Comparison of Analytic Techniques
Authors: Wu Chen-Sen , Latour Lawrence L , Warach Steven
Published: July 2021

P2

Background:
MRI perfusion imaging (PWI) can demonstrate hemodynamic abnormalities in acute stroke. The volume of hypoperfusion derived from calculated perfusion parameter maps has been used to predict tissue at risk for infarction and to identify presumptive ischemic penumbra. It is unclear how best to distinguish true tissue at risk from benign hypoperfusion. A first step toward this goal is identifying clinically significant PWI abnormalities in stroke patients. Our purpose was to evaluate four different perfusion parameter maps to determine which algorithm best correlates with clinical severity.
Methods:
Twenty patients were retrospectively selected from our database. Selection criteria included 1) acute hemispheric lesion, 2) MRI within 24 hours of symptom onset, and 3) no history of prior stroke. Perfusion maps were derived using four different algorithms to estimate relative mean transit time (rMTT): 1) cerebral blood volume (CBV) / cerebral blood flow (CBF), 2) CBV / peak of the concentration-time curve, 3) time to peak (TTP), and 4) ratio of the 1
st
/ 0
th
moment of the transfer function (first moment method). Abnormal perfusion volumes were derived from ever-increasing thresholds of rMTT delay relative to normal contralateral tissue. The volumes at each delay threshold were correlated with National Institutes of Health Stroke Scale (NIHSS) for each algorithm.
Results:
Significant correlations between hypoperfusion volumes and NIHSS were found for all algorithms. The first moment method had the highest correlation (r = 0.76) and the correlations for this method were independent of the delay threshold used to derive the volumes. For the other algorithms, the best correlations were observed for volumes including only voxels with delays of 4 seconds or greater.
Conclusions:
This analysis suggests that the first moment method may have advantages over the others in determining the correlation of hypoperfusion volume to NIHSS. Further analyses correlating acute hypoperfusion volumes to final infarct volumes may help refine the choice of best analytic method for determining clinically relevant PWI abnormalities.
Metro Stroke Task Force Survey of Resources for Diagnosis of Non-Traumatic Subarachnoid Hemorrhage
Authors: Duffy Scott P , Silliman Scott , Brott Thomas G , Richardson Zachery , Wharen Robert , Meschia James F
Published: July 2021

P9

Background:
Up to 25 percent of patients with subarachnoid hemorrhage (SAH)initially receive an incorrect diagnosis. Potential limitations to initially diagnosing SAH include insufficient resources and non-standardized utilization of existing resources. We performed a population-based study to assess adherence to recommendations regarding computed tomography (CT) scanning and cerebrospinal fluid (CSF) analysis as cited in a recent publication.
Methods:
We approached all hospitals with operational emergency departments within a 50 mile radius of downtown Jacksonville, FL. Each facility was contacted by phone or in person by one of two members of the Metro Stroke Task Force (SPD,SS). Included in the survey were groups of questions each directed to a physician or technician best qualified to provide appropriate information. We used the recommendations cited by Edlow and Caplan as a benchmark for diagnosing SAH acutely (cf.
New Engl J Med
2000; 342:29–36). Specifically addressed were the axial imaging slice thickness on head CT and methods for analyzing cerebrospinal fluid for blood and blood products.
Results:
13 of 13 (100%) hospitals responded. 7 of 13 (54%) have 200 or more beds. 10 of 13 (77%) have neurosurgeons on staff. None (0%) of the hospitals surveyed cited a specific protocol for head CT scanning or CSF analysis in the evaluation of suspected subarachnoid hemorrhage. One (7.7%) hospital used CT cuts as thin at the base of the brain as the 3mm recommended. None (0%) of the hospitals routinely used spectrophotometry to evaluate for the presence of xanthochromia in CSF when ruling out SAH.
Conclusion:
We found that there is not a uniform and specific way to approach the diagnosis of SAH among all of the institutions that provide acute care within a 50 mile radius of Jacksonville. Areas for improvement in delivery of care might include standardized protocols for CT acquisition and CSF analysis for blood and blood products. Such standardized measures may reduce the potential for initial diagnostic errors.
Quantitative Measurements of Cerebral Blood Flow in Patients with Unilateral Carotid Artery Occlusion: a PET and MR Study
Authors: Lin Weili , Celik Azim , Derdeyn Colin , An Hongyu , Videen Tom O , Lee Yueh , Ostergaard Leif , Powers William J
Published: July 2021

P15

It has been demonstrated that a quantitative measure of CBF can be obtained with MR when the acquired images are processed by the singular value decomposition (SVD) approach. However, two confounding factors have hampered the success of the SVD approach in clinical settings. First, a constant cardiac output is assumed, potentially leading to variability in the estimates of CBF among subjects. Second, the choice of the arterial input function could be contaminated by partial volume effect. In this study, normal volunteers (n=6) and patients with unilateral carotid artery occlusion (n=5) were studied. In the patient group, rCBF estimates were obtained from both PET and MR. In contrast, only MR estimated rCBF was obtained in the volunteer group. A mean rCBF of 73.6 ± 5.9 ml/100gm/min and 28.1 ± 4.8 ml/100gm/min was obtained for the GM and WM, respectively, in the volunteer group, in excellent agreement with the reported results in the literature via PET. However, when MR estimated rCBF was correlated with those obtained from PET in the patient group, no clear relationships were observed (slope=0.44 and r=0.42, unfilled circles in the figure). This finding is perhaps not surprising given the above mentioned confounding factors associated with the SVD approach. Therefore, a correction factor was derived based on the mean area of the concentration time curves of the superior sagittal sinus from all volunteers. Results are shown in the figure (filled diamonds) after the application of the correction factor. A slope of 1.1 and an r=0.8 was obtained, suggesting that the above mentioned confounding factors can be minimized and a highly linear relationship between the MR and PET estimates of rCBF can be obtained.
A NEW METHOD FOR AUTOMATIC DIFFERENTIATION BETWEEN CEREBRAL EMBOLI AND ARTEFACTS
Authors: Brucher Rainer , Russell David
Published: July 2021

P29

Introduction:
Cerebral embolus monitoring systems suitable for routine clinical use must have the ability to automatically recognise and differentiate between artefacts and emboli. This has to date proven to be an extremely difficult problem to solve.
Methods:
In this study we present a new advancement with regard to the automatic recognition of cerebral emboli and differentiation from artefacts based on a binary decision tree which includes a completely new parameter. This is the 1/4 Doppler shift for the maximum power reflection of an embolic event at 2.5 MHz insonation frequency compared to 2.0 MHz. A new multifrequency transcranial Doppler system together with this software was used in this study of 2000 artefacts and 100 embolic events in one heart valve patient. The level for event recognition was set at 5db above background Doppler power. The artefacts in 2 healthy controls consisted of 200: tapping the probe, 200: tapping the skull, 200: talking (counting), 200: swallowing, 400: coughing, 200: wrinkling the forehead, 200: clenching the teeth, 400: movement of the skin near the probe.
Results:
Only two (skin movements near the probe) of the 2000 artefacts were recognised as embolic events. All 100 heart valve emboli were detected and 98 (98%) were correctly classified (specificity 98%).
Conclusion:
This study suggests that a binary decision tree including 1/4 Doppler shift assessment at 2.0 and 2.5 MHz insonation frequencies will greatly improve the ability to carry out automatic differentiation between artefacts and cerebral emboli during monitoring in routine clinical situations.
Clinical Characteristics of Coronary Heart Disease as Predictors of Ischemic Stroke: A Long-term Prospective Follow-up in the BIP Study.
Authors: Tanne David , Shotan Avraham , Goldbourt Uri , Boyko Valentina , Reicher-Reiss Henrietta , Behar Solomon
Published: July 2021

P126

Objective:
To assess characteristics and severity of coronary heart disease (CHD) predisposing to ischemic stroke, beyond conventional vascular risk factors.
Methods:
We prospectively followed up 3,122 patients with documented CHD included in a secondary prevention trial of lipid modification, the Bezafibrate Infarction Prevention trial. Patients had CHD documented by a history of myocardial infarction ≥6 months and <5 years before enrollment and/or stable angina pectoris confirmed by ancillary diagnostic testing, and a selected lipid profile. Patients with severe heart failure or unstable angina upon enrollment were excluded.
Results:
During a mean follow-up period of 8.2 years, 186 patients developed an ischemic stroke. The rate of ischemic stroke was 8.8% among patients with an active anginal syndrome[class ≥2 according to the Canadian Cardiovascular Society angina Classification, (CCSC)]vs. 5.1% in patients with a CCSC class of 1 (p<0.001). Patients with heart failure according to class ≥2 of the New York Heart Association classification had a 7.7% rate of ischemic stroke vs. 5.5% among patients with a class of 1 (no limitation of physical activity; p=0.03). In a Cox Proportional Hazard model adjusting for conventional risk factors, CCSC angina class ≥2 remained an independent predictor of ischemic stroke (Hazard ratio 1.43; 95%CI 1.05–1.96) and hospitalization for a confirmed diagnosis of unstable angina during follow-up conferred an additional independent increased risk (Hazard ratio 1.7; 95%CI 1.04–2.87). Hazard ratios of conventional risk factors, for comparison, where 1.49 for a 10 year age increment, 2.29 for diabetes mellitus, 1.75 for current smoking, 1.81 for peripheral vascular disease, and 1.14 for a 10 mmHg increase in systolic blood pressure.
Conclusion:
Active angina (CCSC class ≥2)and hospitalization for unstable angina during follow-up among CHD patients,confer an independent increased risk of ischemic stroke, beyond conventional vascular risk factors.
Plaques in the carotid artery and risk of cerebral infarcts in the elderly; The Rotterdam Study
Authors: Hollander Monika , Bots Michiel L , Witteman Jacqueline Cm , Koudstaal Peter J , Grobbee Diederick E , Hofman Albert , Breteler Monique Mb
Published: July 2021

P132

Background
Presence of carotid plaques is associated with increased risk of cerebral infarcts. Whether they directly cause a stroke through embolism or merely are indicators of generalised atherosclerosis is not extensively investigated. We studied this by assessing the association between plaques at different carotid segments and risk of subtypes of cerebral infarcts.
Methods
Our study is based on 5444 subjects from the Rotterdam Study, a population based cohort study. Subjects were free from previous stroke. Presence of plaques was assessed in 3 segments of both carotid arteries at baseline (1990–1993). A total plaque score reflected the number of locations with plaques (range 0–6). Follow up for stroke was complete until December 31 1997. We calculated the risk of severe plaques (score 5–6) compared to absence of plaques (score 0) by Cox regression, adjusting for age and gender. Furthermore, we analysed the risk of unilateral and bilateral plaques compared to absence of plaques at different segments of the carotid artery. Relative risks (95% CI) are given for subtypes of cerebral infarct.
Results
In total 224 strokes occurred of whom 130 were ischemic. Severe plaques were present in 7% of the population and associated with an increased risk of lacunar and anterior circulation infarcts (RR 12.0 (2.0–70) and 4.5 (1.6–12.3), respectively). After exclusion of infarcts of presumed cardio-embolic cause the relative risk of anterior circulation infarcts was 9.4 (2.5–35.7). The risk for bilateral plaques was higher than for unilateral plaques when we analysed carotid segments separately. We found no association between severe plaques and risk of posterior circulation infarcts.
Conclusion
Carotid plaques are associated with increased risk of lacunar and anterior circulation infarcts. Associations were stronger with increasing number of plaques. This suggests that carotid plaques are markers of atherosclerosis on large and small vessel level. Since we found no association with posterior circulation infarcts it seems likely that at least part of the effect is through thrombo-embolism.
Silent Brain MRI Infarcts and Subsequent Stroke Type In the Cardiovascular health Study
Authors: Bernick Charles B , Kuller Lewis H , Longstreth Will T , Dulberg Corinne , Manolio Teri A , Beauchamp Norman J , Price Thomas R
Published: July 2021

P136

Objective:
Silent infarcts seen on cranial MRI scans are a risk factor for subsequent clinical stroke in the elderly. This study examines the type of clinical strokes seen in those with silent infarcts.
Methods:
Cranial MRI examination was completed on 3324 Cardiovascular Health Study (CHS) participants aged 65+ who were without a prior history of clinical stroke. Incident strokes were identified over an average follow-up of 4 years and classified as hemorrhagic or ischemic. Ischemic strokes were further subdivided into lacunar, cardioembolic, atherosclerotic or other/unknown.
Results:
Silent MRI infarcts >3mm were found in approximately 28% (n=923). Of these, 7% (n=67) subsequently had a clinically evident stroke. The characteristics of the silent MRI infarcts in those who sustained an incident stroke were as folows: 56 had only subcortical infarcts, of which 55 were <20mm; 4 had only cortical infarcts; and 7 had both cortical and subcortical infarcts. Of those with only subcortical silent MRI infarcts, 16% (n=9) went on to a hemorrhagic stroke and 84% (n=47) sustained an ischemic stroke. The ischemic strokes were subtyped as 12 cardioembolic, 3 lacunar, 2 atherosclerotic and 30 unknown/other. Considering only those with cortical silent infarcts, either alone or in combination with subcortical infarcts, there was 1 hemorrhagic stroke and 10 ischemic strokes. Half of the ischemic strokes were cardioembolic and half were unknown type.
Conclusion:
Elderly individuals with silent subcortical infarcts who go onto subsequent stroke may be at risk not only for lacunar infarcts but also cardioembolic or hemorrhagic strokes.
Mild-to-moderate hyperhomocyst(e)inemia and risk of stroke. Result of a meta-analysis.
Authors: Kelly Peter J , Rosand Jonathan , Plomaritoglou Androniki , Chang Yuchiao , Kistler J Philip , Furie Karen L
Published: July 2021

P148

Background:
Severe hyperhomocyst(e)inemia is associated with premature atherothrombosis and stroke in children with homocystinuria. Epidemiological studies indicate that mild-to-moderate hyperhomocyst(e)inemia is an independent risk factor for coronary artery disease. However, data are conflicting concerning the risk of stroke associated with mild-to-moderate hyperhomocyst(e)inemia. Aim: To describe and quantify the risk of stroke associated with elevated plasma homocyst(e)ine by meta-analysis.
Methods:
Relevant articles were obtained by search of Medline, Science Citation Index, and abstracts of conference proceedings. Search terms were Homocysteine, stroke, genetics and MTHFR. Exposure was defined as hyper-homocyst(e)inemia, relative to control values in each study population. Outcome was defined as ischemic stroke confirmed by neuroimaging (NI), and stroke without NI. Inclusion criteria: (1) Case-control (C-C) studies with reported odds ratios (OR) (2) Cohort (COH) studies with reported risk ratios (RR). Exclusion criteria: (1) Studies without clearly-defined OR/RR (reviews, C-C without OR, cross-sectional studies, case series, case reports) (2) Studies which defined outcome as carotid atherosclerosis or intima-media thickening. Statistical analyses for between-study heterogeneity and pooled risk estimates were performed using Stata software©.
Results:
Of 35 studies analyzed in detail, 15 (2 COH, 13 C-C) met inclusion criteria. Of 13 C-C studies (1306 cases, 6793 controls), the adjusted OR ranged 0.99–4.7, two had adjusted OR <=1 and 5 had a lower confidence limit <1. A random-effects model estimated a weighted pooled adjusted OR of 1.69 (95% CI 1.3, 2.2) from the 13 C-C studies. Within the 2 cohort studies (2825 subjects), the average adjusted RR was 1.86 (upper vs lower quantiles) (95% CI 1.14, 3.03).
Conclusions:
On average, mild-moderate hyperhomocyst(e)inemia is independently associated with a 69% increase in the odds and 86% increase in the risk of stroke.
Neuroprotection for acute ischemic stroke: Who is most to blame for current failure ?
Authors: Davalos Antonio , Castillo Jose , Chamorro Angel
Published: July 2021

P179

Neuroprotection has so far proved disappointing in acute ischemic stroke. However, neither clinical nor biological cues of ongoing neurotoxicity were provided in previous phase III trials. Thus it remains unsettled whether faulty drug selection, inadequate patients′ traits, or both, explain treatment failure. In 258 patients with first ever acute hemispheric ischemic stroke we found that admission plasma concentrations of glutamate >200 μmol/L (OR, 26.1; 95%CI, 6.9 to 98.6), interleukin-6 >21.5 pg/mL (OR, 14.9; 95%CI, 4.4 to 50.8), and GABA <190 nmol/L (OR,5.5; 95%CI, 3.2 to 9.7), and NO-metabolites >5.0 μmol/mL in CSF (OR, 5.3; 95%CI, 1.5 to 18.5), were sensitive and specific independent predictors of patients at high-risk of early neurologic deterioration regardless of infarction topography, size, and mechanism. Sensitivity and specificity values are given in the table. Early neurologic deterioration is a harbinger of impending poor outcome that in many instances we could forecast using the aforementioned tests. As early neurologic deterioration most commonly reflects those molecular events that neuroprotectants are aimed to prevent, we advocate to include it as a primary end-point in forthcoming neuroprotectant trials. We also contend to launch large and expensive trials once smaller studies restricted to patients at high-risk of early worsening have disclosed laboratory indications of neuroprotection.
Early administration of high-dose IV unfractionated heparin blunts sVCAM-1 and improves functional outcome more effectively than 300 mg oral aspirin in acute ischemic stroke.
Authors: Chamorro Angel , Castillo Jose , Davalos Antonio
Published: July 2021

P186

Methods:
We studied prospectively 167 patients with ischemic stroke (58% males, 67.7± 9.8 years) that received 1000 IU/h i.v. unfractionated heparin (UFH) (n=70) or 300 mg oral aspirin (n=97) at a mean treatment delay of 6.7 hours (95% CI 5.9–7.4). Baseline and 48 hours plasma levels of IL-6, IL-10, IL-4, TNF-α, sICAM-1, and sVCAM-1 were compared in both treatment groups. All patients had baseline and follow up CT scans, and stroke diagnosis followed TOAST criteria. Multivariate analyses adjusting for confounders assessed the impact of cytokines and adhesion factors on the Barthel Index (BI) score at 6 months.
Results:
Whereas TNF-α, and sICAM-1 decreased at follow-up, IL-6, IL-4, and sVCAM-1 increased compared to baseline values (all p<0.01). sVCAM-1 levels, adjusted for baseline inflammatory levels, neurological impairment, and CT findings were significantly lower at follow-up in patients treated with UFH (p=0.01). Other inflammatory markers did not differ between aspirin and UFH. Independent predictors of poor outcome (BI < 85) included 5 mm Hg increase in MAP (OR 1.16, 1.01–1.33), early CT signs of infarction (OR 8.30, 2.8–24.64), 1°C increase in body temperature (OR 3.23, 1.58–6.6), 1 point decrease in the Canadian Stroke Scale (OR 1.66, 1.31–2.12), and a twofold increase at 48 hours of baseline sVCAM-1(OR 2.19,1.1–4.39).
Conclusions:
The rise of sVCAM-1 is an independent predictor of clinical outcome at 6 months in patients with ischemic stroke. sVCAM-1 is more effectively decreased with high-dose UFH than with aspirin. To confirm that shorter heparin delay, IV route, and high-dose are required to blunt inflammation and improve functional outcome more effectively than aspirin in ischemic stroke a multinational trial has been organized, the Rapid Anticoagulation Prevents Ischemic Damage (RAPID) study.
Passive Retrograde Cerebral Perfusion (PRCP)Following Routine Cardiac Valve Surgery Eliminates the Risk of Peri-Operative Cerebral Vascular Accidents
Authors: Quigley Robert L , Fried David W , Kramer Jan. L , Highbloom Richard Y , Pym John , Weiss Steven J , Gonzalez Janet
Published: July 2021

P215

A post-operative neurologic event, in the open heart patient, is second only to a low cardiac output state as the complication most highly associated with in-hospital death. In the elderly, the incidence of a cerebral vascular accident (CVA), following cardiac valve surgery in particular, may be as high as 11%. This may be the result of either macro-embolism (air/debris) or inadequate perfusion pressure. We have previously demonstrated in a cohort of valve patients that upon discontinuation of cardiopulmonary bypass (CPB) the risk of peri-operative stroke could virtually be eliminated by opening a shunt for three minutes between the arterial (in-flow) and venous (out-flow) limbs of the extra-corporeal circuit. This phenomenon, passive retrograde cerebral perfusion (PRCP), reverses blood flow in the middle cerebral arteries. In this study, we have further evaluated PRCP in an older population with more co-morbidities to determine if there exists any limitations to the procedure. One hundred eight consecutive patients with a mean age of 68 years (range 38- 90 years) underwent elective valve repair/replacement and PRCP was instituted. The mean shunt flow rate was 2.6 Liters/minute (L/m) with a range of 1.9–4.0 L/m. The incidence of peri-operative CVA (30 day) was 0% (0/108). The incidence of CVA in published retrospective data is 0.7–3.8% and 4.8–5.2% in prospective data. In this report, we confirm that PRCP following valve surgery eliminates the risk of peri-operative CVA. We frequently perform the procedure as an adjunct to on-pump coronary artery bypass surgery in the context of suspected intra-ventricular thrombus or an artheromatous ascending aorta. We hypothesize that the principles of PRCP could easily be applied to Port surgery now that the instrumentation is trans-thoracic since aortic occlusion is still performed with an intra-vascular device.
Abstract 114: Neuroprotective Role of Brain Pericytes through PDGFRβ-Akt Signaling in Ischemic Stroke
Authors: Arimura Koichi , Ago Tetsuro , Kamouchi Masahiro , Sugimori Hiroshi , Kuroda Junya , Ishitsuka Koji , Sasaki Tomio , Kitazono Takanari
Published: July 2021

Brain pericytes are a constituent of the neurovascular unit and play various important roles in brain functions, such as regulation of capillary blood flow, maintenance of blood-brain barrier and angiogenesis. Previous reports have elucidated that PDGF-B prevents neuronal cell death during ischemic insults in adult rodent models; however, the detailed mechanisms by which PDGF-B signaling protects neurons from ischemic damage are not fully understood. In the present study, we investigated whether brain pericytes play neuroprotective roles in brain ischemia, using a permanent middle cerebral artery occlusion stroke model (MCAO) and cultured human brain pericytes. Immunohistochemistry revealed that the expression of PDGF receptorβ(PDGFRβ) was induced predominantly in pericytes in peri-infarct areas. PDGF-B induced marked phosphorylation of Akt in cultured pericytes. Consistently, Akt was markedly phosphorylated in the PDGFRβ-expressing pericytes in peri-infarct areas. PDGF-B upregulated the expression of neurotrophins, such as neuronal growth factor (NGF) and neurotrophin-3 (NT-3), through Akt activation in the cultured pericytes. We subjected PDGFRβheterozygous knockout (PDGFRβ+/-) mice to MCAO. Infarct volume, as assessed by MAP2 immunostaining, was significantly greater in PDGFRβ+/- than wild-type mice ( 48% increase at day 7, p < 0.01 , n=5). The number of TUNEL positive apoptotic cells was significantly greater in PDGFRβ+/- mice (54 % increase at day 4, p < 0.001 , n=6). Production of NGF and NT-3 at mRNA and protein levels in infarct areas was significantly decreased in PDGFRβ+/- mice (NGF: 28% decrease, p<0.05, NT-3: 22% decrease, p<0.05). Since it has been established that neurotrophin receptors are induced in peri-infarct areas, the decreases in neurotrophin production may increase apoptotic neuronal cell death in the PDGFRβ+/- mice. In conclusion, brain pericytes may have a direct neuroprotective role through secreting neurotrophins via PDGFRβ-Akt signaling, thereby decreasing infarct volume in ischemic stroke.
Abstract 131: Continuous Stroke Unit ECG Monitoring is better than 24-h Holter ECG for Detection of Paroxysmal Atrial Fibrillation after Stroke
Authors: Veltkamp Roland , Guentner Janina , Jenetzky Ekkehart , Becker Ruediger , Kirchhof Paulus , Reinhardt Roland , Hepp Thomas , Hacke Werner , Rizos Timolaos
Published: July 2021

Background and purpose:
Cardioembolism in paroxysmal atrial fibrillation (pxAF) is a frequent cause of ischemic stroke (IS). Sensitive detection of pxAF after stroke is crucial for adequate secondary stroke prevention; the optimal diagnostic modality is unknown. To compare 24h-Holter ECG, the standard tool to detect pxAF, with continuous stroke unit ECG monitoring (CEM) for pxAF detection.

Methods:
Prospective single centre study of consecutive patients with acute IS or transient ischemic attack (TIA) admitted to a stroke unit of a tertiary hospital. Main outcome measures: Yield of pxAF detection by 12-channel ECG on admission, admission ECG plus 24h-Holter ECG, admission ECG plus CEM and admission ECG plus automated analysis of ECG monitoring data using a dedicated software to identify pxAF (aCEM).

Results:
579 patients (median age 71, 59.8% male) fulfilled predefined inclusion criteria (IS: 81.3%; TIA: 18.7%). Median stroke unit stay lasted 89.8h (65.5-122.5). ECG data for aCEM analysis were available for a median time of 64h (43-91). In 130 patients (22.5%) AF was diagnosed; of which 73 (12.6%) showed persistent AF and 57 (9.8%) pxAF. Admission ECG discovered pxAF in 16/57 (28.1%). Admission ECG plus 24h-Holter ECG identified 31/57 (54.4%). Admission ECG plus CEM without automated analysis was significantly more effective (40/57; 70.1%) than admission ECG plus 24h-Holter ECG. Combining admission ECG and aCEM provided an even better detection rate (55/57; 96.5%; p<0.001).

Conclusions:
CEM can replace 24h-Holter ECGs as the standard procedure for evaluation for pxAF on stroke units.
Abstract 134: Endovascular Revascularization Is Associated With Better Outcomes Than Systemic Throbmolysis Alone For Tandem Internal Carotid And Middle Cerebral Artery Occlusion
Authors: Pepper Joshua , Pashankar Rashmi , Schindler Joseph , Bulsara Ketan
Published: July 2021

Background and Purpose:
Tandem Internal Carotid Artery and Middle Cerebral Artery or “TIM” occlusions are highly resistant to conventional therapy (systemic thrombolysis) and independently predicts poor patient outcome. Recent evidence suggests that patients treated more aggressively with either endovascular stenting of occluded carotid arteries and/or intra-arterial tissue plasminogen activator (tPA) may have superior outcomes. Here we evaluate all the available data to help assess the best intervention for this patient population that currently has limited treatment options.

Methods:
Data from Medline and the Cochrane database of systemic reviews was searched. The search terms used includes (tandem OR combined) AND (middle cerebral OR internal carotid) AND (OCCLU* or lesion or stenos* or blocka*). All studies had to be in English. All duplicates were identified and removed. To be included the studies needed to report on three key aspects: 1) baseline characteristics (age; NIHSS at presentation); 2) treatment (time to treatment; modality); and 3) outcome (report of patient state at discharge or follow up on the Modified Rankin Scale). Patients were grouped according to whether they received endovascular intervention or stand alone IV tPA. Patients were considered independent if they had a Modified Rankin Scale score of ≤ 2 at follow up or discharge.

Results:
Over 2,500 studies were evaluated. Seventeen studies met the inclusion criteria, with a total of 219 patients. Patients treated with endovascular therapy (n=60) (stenting and/or intra-arterial tPA) were 32% more likely to be independent (p<0.0001) and 28% less likely to have a significant disability (p= 0.0004) compared to patients given systemic thrombolysis (n=139). There was no significant difference in mortality or complication rates between the groups.

Conclusion:
Endovascular therapy appears to be superior compared with systemic thrombolysis in treating patients with TIM occlusions. The risk of iatrogenic complications with more aggressive intervention does not appear to outweigh the outcome benefit. Further and larger studies are needed to assess the benefits and risks of endovascular therapy in patients with TIM lesions.