Cerebral blood flow and neurocognition in patients undergoing transcatheter aortic valve replacement for severe aortic stenosis.

Aims: Aortic valve stenosis (AS) results in higher systolic pressure to overcome resistance from the stenotic valve, leading to heart failure and decline in cardiac output. There has been no assessment of cerebral blood flow (CBF) association with neurocognition in AS or the effects of valve replacement. The goal was to determine if AS is associated with altered cerebral haemodynamics and impaired neurocognition, and whether transcatheter aortic valve replacement (TAVR) improves haemodynamics and cognition. Methods and results: In 42 patients with planned TAVR, transcranial Doppler (TCD) assessed bilateral middle cerebral artery (MCA) mean flow velocities (MFVs); abnormality was <34.45 cm/s. The neurocognitive battery assessed memory, language, attention, visual-spatial skills, and executive function, yielding a composite Z-score. Impairment was <1.5 SDs below the normative mean. The mean age was 78 years, 59% Male, and the mean valve gradient was 46.87 mm/Hg. Mean follow-up was 36 days post-TAVR (range 27-55). Pre-TAVR, the mean MFV was 42.36 cm/s (SD = 10.17), and the mean cognitive Z-score was -0.22 SDs (range -1.99 to 1.08) below the normative mean. Among the 34 patients who returned after TAVR, the MFV was 41.59 cm/s (SD = 10.42), not different from baseline (P = 0.66, 2.28-3.67). Post-TAVR, average Z-scores were 0.17 SDs above the normative mean, not meeting the pre-specified threshold for a clinically significant 0.5 SD change. Conclusion: Among patients with severe AS, there was little impairment of MFV on TCD and no correlation with cognition. Transcatheter aortic valve replacement did not affect MFV or cognition. Assumptions about diminished CBF and improvement after TAVR were not supported.

Educational Intervention in the Emergency Department to Address Disparities in Stroke Knowledge.

OBJECTIVES: In the United States, Black individuals have higher stroke incidence and mortality when compared to white individuals and are also at risk of having lower stroke knowledge and awareness. With the need to implement focused interventions to decrease stroke disparities, the objective of this study is to evaluate the feasibility and efficacy of an emergency department-based educational intervention aimed at increasing stroke awareness and preparedness among a disproportionately high-risk group. MATERIALS AND METHODS: Over a three-month timeframe, an emergency department-based, prospective educational intervention was implemented for Black patients in an urban, academic emergency department. All participants received stroke education in the forms of a video, written brochure and verbal counseling.  Stroke knowledge was assessed pre-intervention, immediately post-intervention, and at one-month post-intervention. RESULTS: One hundred eighty-five patients were approached for enrollment, of whom 100 participants completed the educational intervention as well as the pre- and immediate post- intervention knowledge assessments. Participants demonstrated increased stroke knowledge from baseline knowledge assessment (5.35 ± 1.97) at both immediate post-intervention (7.66 ± 2.42, p < .0001) and one-month post-intervention assessment (7.21 ± 2.21, p < .0001). CONCLUSIONS: Emergency department-based stroke education can result in improved knowledge among this focused demographic. The emergency department represents a potential site for educational interventions to address disparities in stroke knowledge.

Erratum: Race and in-hospital mortality after spontaneous intracerebral hemorrhage in the Stroke Belt: Secondary analysis of a case-control study - CORRIGENDUM.

[This corrects the article DOI: 10.1017/cts.2021.21.].

Trauma Communications Center Coordinated Severity-Based Stroke Triage: Protocol of a Hybrid Type 1 Effectiveness-Implementation Study.

Background: Mechanical thrombectomy (MT) can improve the outcomes of patients with large vessel occlusion (LVO), but a minority of patients with LVO are treated and there are disparities in timely access to MT. In part, this is because in most regions, including Alabama, the emergency medical service (EMS) transports all patients with suspected stroke, regardless of severity, to the nearest stroke center. Consequently, patients with LVO may experience delayed arrival at stroke centers with MT capability and worse outcomes. Alabama's trauma communications center (TCC) coordinates EMS transport of trauma patients by trauma severity and regional hospital capability. Our aims are to develop a severity-based stroke triage (SBST) care model based on Alabama's trauma system, compare the effectiveness of this care pathway to current stroke triage in Alabama for improving broad, equitable, and timely access to MT, and explore stakeholder perceptions of the intervention's feasibility, appropriateness, and acceptability. Methods: This is a hybrid type 1 effectiveness-implementation study with a multi-phase mixed methods sequential design and an embedded observational stepped wedge cluster trial. We will extend TCC guided stroke severity assessment to all EMS regions in Alabama; conduct stakeholder interviews and focus groups to aid in development of region and hospital specific prehospital and inter-facility stroke triage plans for patients with suspected LVO; implement a phased rollout of TCC Coordinated SBST across Alabama's six EMS regions; and conduct stakeholder surveys and interviews to assess context-specific perceptions of the intervention. The primary outcome is the change in proportion of prehospital stroke system patients with suspected LVO who are treated with MT before and after implementation of TCC Coordinated SBST. Secondary outcomes include change in broad public health impact before and after implementation and stakeholder perceptions of the intervention's feasibility, appropriateness, and acceptability using a mixed methods approach. With 1200 to 1300 total observations over 36 months, we have 80% power to detect a 15% improvement in the primary endpoint. Discussion: This project, if successful, can demonstrate how the trauma system infrastructure can serve as the basis for a more integrated and effective system of emergency stroke care.

Race and in-hospital mortality after spontaneous intracerebral hemorrhage in the Stroke Belt: Secondary analysis of a case-control study.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) accounts for around 10% of stroke, but carries 50% of stroke mortality. ICH characteristics and prognostic factors specific to the Stroke Belt are not well defined by race. METHODS: Records of patients admitted to the University of Alabama Hospital with ICH from 2017 to 2019 were reviewed. We examined the association of demographics; clinical and radiographic features including stroke severity, hematoma volume, and ICH score; and transfer status with in-hospital mortality and discharge functional status for a biracial population including Black and White patients. Independent predictors of in-hospital mortality and functional outcome were examined using logistic regression. RESULTS: Among the 275 ICH cases included in this biracial analysis, Black patients (n = 114) compared to White patients (n = 161) were younger (60.6 vs. 71.4 years, P < 0.0001), more often urban (81% vs. 64%, P < 0.01), more likely to have a history of hypertension (87% vs. 71%, P < 0.01), less often transferred (44% vs. 74%, P < 0.01), and had smaller median initial hematoma volumes (9.1 vs. 12.6 mL, P = 0.041). On multivariable analysis, Glasgow Coma Scale (GCS) for White patients (OR 13.0, P < 0.0001), hyperlipidemia for Black patients (OR 13.9, P = 0.019), and ICH volume for either race (Black patients: OR 1.05, P = 0.03 and White patients: OR 1.04, P < 0.01) were independent predictors of in-hospital mortality. CONCLUSIONS: Hypertension is more prevalent among Black ICH patients in the Stroke Belt. The addition of hyperlipidemia to the ICH score model improved the prediction of mortality for Black ICH patients. No differences in in-hospital mortality or poor functional outcome were observed by race.

A Novel Combination of Blood Biomarkers and Clinical Stroke Scales Facilitates Detection of Large Vessel Occlusion Ischemic Strokes.

Acute ischemic stroke caused by large vessel occlusions (LVOs) is a major contributor to stroke deaths and disabilities; however, identification for emergency treatment is challenging. We recruited two separate cohorts of suspected stroke patients and screened a panel of blood-derived protein biomarkers for LVO detection. Diagnostic performance was estimated by using blood biomarkers in combination with NIHSS-derived stroke severity scales. Multivariable analysis demonstrated that D-dimer (OR 16, 95% CI 5-60; p-value < 0.001) and GFAP (OR 0.002, 95% CI 0-0.68; p-value < 0.05) comprised the optimal panel for LVO detection. Combinations of D-dimer and GFAP with a number of stroke severity scales increased the number of true positives, while reducing false positives due to hemorrhage, as compared to stroke scales alone (p-value < 0.001). A combination of the biomarkers with FAST-ED resulted in the highest accuracy at 95% (95% CI: 87-99%), with sensitivity of 91% (95% CI: 72-99%), and specificity of 96% (95% CI: 90-99%). Diagnostic accuracy was confirmed in an independent cohort, in which accuracy was again shown to be 95% (95% CI: 87-99%), with a sensitivity of 82% (95% CI: 57-96%), and specificity of 98% (95% CI: 92-100%). Accordingly, the combination of D-dimer and GFAP with stroke scales may provide a simple and highly accurate tool for identifying LVO patients, with a potential impact on time to treatment.

Restoration of CTSD (cathepsin D) and lysosomal function in stroke is neuroprotective.

Stroke is a leading cause of death and disability. The pathophysiological mechanisms associated with stroke are very complex and not fully understood. Lysosomal function has a vital physiological function in the maintenance of cellular homeostasis. In neurons, CTSD (cathepsin D) is an essential protease involved in the regulation of proteolytic activity of the lysosomes. Loss of CTSD leads to lysosomal dysfunction and accumulation of different cellular proteins implicated in neurodegenerative diseases. In cerebral ischemia, the role of CTSD and lysosomal function is not clearly defined. We used oxygen-glucose deprivation (OGD) in mouse cortical neurons and the middle cerebral artery occlusion (MCAO) model of stroke to assess the role of CTSD in stroke pathophysiology. Our results show a time-dependent decrease in CTSD protein levels and activity in the mouse brain after stroke and neurons following OGD, with concurrent defects in lysosomal function. We found that shRNA-mediated knockdown of CTSD in neurons is sufficient to cause lysosomal dysfunction. CTSD knockdown further aggravates lysosomal dysfunction and cell death in OGD-exposed neurons. Restoration of CTSD protein levels via lentiviral transduction increases CTSD activity in neurons and, thus, renders resistance to OGD-mediated defects in lysosomal function and cell death. This study indicates that CTSD-dependent lysosomal function is critical for maintaining neuronal survival in cerebral ischemia; thus, strategies focused on maintaining CTSD function in neurons are potentially novel therapeutic approaches to prevent neuronal death in stroke.Abbreviations: 3-MA: 3-methyladenine; ACTB: actin beta; AD: Alzheimer disease; ALS: amyotrophic lateral sclerosis; CQ: chloroquine; CTSB: cathepsin B; CTSD: cathepsin D; CTSL: cathepsin L; FTD: frontotemporal dementia, HD: Huntington disease; LAMP1: lysosomal associated membrane protein 1; LSD: lysosomal storage disease; MCAO: middle cerebral artery occlusion; OGD: oxygen glucose deprivation; OGR: oxygen glucose resupply; PD: Parkinson disease; SQSMT1: sequestosome 1; TCA: trichloroacetic acid; TTC: triphenyl tetrazolium chloride.

Centrally Guided Identification of Patients With Large Vessel Occlusion: Lessons From Trauma Systems.

OBJECTIVE: Improve prehospital identification of acute ischemic stroke patients with large vessel occlusion (LVO) by using a trauma system-based emergency communication center (ECC) to guide the emergency medical service (EMS). METHODS: We trained 24 ECC paramedics in the Emergency Medical Stroke Assessment (EMSA). ECC-guided EMS in performance of the EMSA on patients with suspected stroke. During the second half of the study, we provided focused feedback to ECC after reviewing recorded ECC-EMS interactions. We compared the sensitivity, specificity, and area under the receiver operator characteristics curve (AUC) and 95% confidence interval of ECC-guided EMSA to the NIH Stroke Scale (NIHSS) for predicting a discharge diagnosis of LVO. RESULTS: We enrolled 569 patients from September 2016 through February 2018. Of 463 patients analyzed, 236 (51%) had a discharge diagnosis of stroke and 227 (49%) had a nonstroke diagnosis. There were 45 (19%) stroke patients with LVO. For predicting LVO, there was no significant difference between the EMSA AUC = .68 (.59-.77) and the NIHSS AUC = .73 (.65-.81). An EMSA score greater than or equal to 4 had sensitivity = 75.6 (60.5-87.1) and specificity = 62.4 (57.6-67.1) for LVO. During the first 9 months of the study, the EMSA AUC = .61 (.44-.77) compared to an AUC = .74 (.64-.84) during the second 9 months. CONCLUSIONS: ECC-guided prehospital EMSA is feasible, has similar ability to predict LVO compared to the NIHSS, and has sustained performance over time.

Admission Systolic Blood Pressure Predicts the Number of Blood Pressure Medications at Discharge in Patients With Primary Intracerebral Hemorrhage.

BACKGROUND: Control of systolic blood pressure (SBP) after primary intracerebral hemorrhage improves outcomes. Factors determining the number of blood pressure medications (BPM) required for goal SBP<160 mm Hg at discharge are unknown. We hypothesized that higher admission-SBPs require a greater number of BPM for goal discharge-SBP<160 mm Hg, and investigated factors influencing this goal. MATERIALS AND METHODS: We conducted a retrospective review of 288 patients who presented with primary intracerebral hemorrhage. Admission-SBP was obtained. Primary outcome was the number of BPM at discharge. Comparison was made between patients presenting with and without a history of hypertension, and patients discharged on <3 and ≥3 BPM. RESULTS: Patients with hypertension history had a higher median admission-SBP compared with those without (180 vs. 157 mm Hg, P=0.0001). In total, 133 of 288 (46.2%) patients were discharged on <3 BPM; 155/288 (53.8%) were discharged on ≥3 BPM. Hypertension history (P<0.0001) and admission-SBP (P<0.0001) predicted the number of BPM at discharge. In patients without hypertension history, every 10 mm Hg increase in SBP resulted in an absolute increase of 0.5 BPM at discharge (P=0.0011), whereas in those with hypertension, the absolute increase was 1.3 BPM (P=0.0012). In comparison with patients discharged on <3 BPM, patients discharged on ≥3 BPM were more likely to have a higher median admission-SBP, be younger in age, belong to the African-American race, have a history of diabetes, have higher median admission-National Institutes of Health Stroke Scale and modified Rankin Scale of 4 to 5 at discharge. CONCLUSIONS: An understanding of the factors influencing BPM at discharge may help clinicians better optimize blood pressure control both before and after discharge.

Derivation and Validation of the Emergency Medical Stroke Assessment and Comparison of Large Vessel Occlusion Scales.

BACKGROUND: This study aims to develop a simple scale to identify patients with prehospital stroke with large vessel occlusion (LVO), without losing sensitivity for other stroke types. METHODS: The Emergency Medical Stroke Assessment (EMSA) was derived from the National Institutes of Health Stroke Scale (NIHSS) items and validated for prediction of LVO in a separate cohort. We compared the EMSA with the 3-item stroke scale (3I-SS), Cincinnati Prehospital Stroke Severity Scale (C-STAT), Rapid Arterial oCclusion Evaluation (RACE) scale, and Field Assessment Stroke Triage for Emergency Destination (FAST-ED) for prediction of LVO and stroke. We surveyed paramedics to assess ease of use and interpretation of scales. RESULTS: The combination of gaze preference, facial asymmetry, asymmetrical arm and leg drift, and abnormal speech or language yielded the EMSA. An EMSA less than 3, 75% sensitivity, and 50% specificity significantly reduced the likelihood of LVO (LR- = .489, 95% confidence interval .366-0.637) versus 3I-SS less than 4 (.866, .798-0.926). A normal EMSA, 93% sensitivity, and 47% specificity significantly reduced the likelihood of stroke (LR- = .142, .068-0.299) versus 3I-SS (.476, .330-0.688) and C-STAT (.858, .717-1.028). EMSA was rated easy to perform by 72% (13 of 18) of paramedics versus 67% (12 of 18) for FAST-ED and 6% (1 of 18) for RACE (χ2 = 27.25, P < .0001), and easy to interpret by 94% (17 of 18) versus 56% (10 of 18) for FAST-ED and 11% (2 of 18) for RACE (χ2 = 21.13, P < .0001). CONCLUSIONS: The EMSA has superior abilities to identify LVO versus 3I-SS and stroke versus 3I-SS and C-STAT. The EMSA has similar ability to triage patients with stroke compared with the FAST-ED and RACE, but is simpler to perform and interpret.

Factors related to the sensitivity of emergency medical service impression of stroke.

OBJECTIVES: To examine factors related to sensitivity of emergency medical services (EMS) stroke impression. METHODS: We reviewed ambulance and hospital records of all patients transported to Long Island College Hospital between January 1, 2009 and January 1, 2011 by the hospital-based EMS with a discharge diagnosis of stroke or a confounding diagnosis, and compared EMS impression to hospital discharge diagnosis. We examined relationships between EMS diagnostic sensitivity and age, gender, ethnicity, NIH Stroke Scale (NIHSS), motor signs, aphasia, neglect, lesion side, circulation, stroke type, EMS provider level, and documented Cincinnati Pre-hospital Stroke Scale (CPSS) with contingency analysis and logistic regression. RESULTS: Stroke was validated in 18% (56/310) of patients and 50% (28/56) of these were missed by EMS. EMS diagnostic sensitivity was 50% (95% CI: 36-64%), and was related to NIHSS quartile (p = 0.014), with higher sensitivities in 2nd (69%; 95% CI: 44-86%) and 3rd (75%; 95% CI: 47-91%) vs. 1st (20%; 95% CI: 7-45%) and 4th (45%; 95% CI: 21-72%) quartiles, motor signs (62 vs. 14%, p = 0.002), and documented CPSS (84 vs. 32%, p = 0.0002). EMS impression was independently related to NIHSS quartile (1st vs. 2nd adjusted OR = 9.61, 1.13-122.03, p = 0.038) and CPSS (adjusted OR = 12.58, 2.22-111.06, p = 0.003). CONCLUSION: Stroke was missed more frequently when CPSS was not documented, in patients without motor signs, and in patients with moderate-severe stroke. The sensitivity of prehospital screening for patients with moderate-severe stroke might be improved by including additional non-motor signs and by stressing indications for when screens should be performed.

Cardiac papillary fibroelastoma originating from pulmonary vein--a case report.

Cardiac papillary fibroelastoma is a primary cardiac neoplasm that typically affects the cardiac valves, mainly the aortic and mitral valves, and very rarely the endocardium of cardiac chambers. Cardiac papillary fibroelastoma is rarely diagnosed during life, as the majority are incidental findings at autopsy, but with the advent of echocardiography, it is being increasingly recognized. Although the tumor is usually small and histologically benign, it may have a malignant propensity for life-threatening complications, such as a cerebrovascular accident, myocardial ischemia or infarction, or sudden death. The patient reported here presented with an embolic stroke from a thrombus on the surface of a left atrial papillary fibroelastoma. The papillary fibroelastoma was originating from the lower portion of the left inferior pulmonary vein and was protruding into the left atrial cavity. Papillary fibroelastoma originating from the pulmonary veins has not been reported before. The tumor was successfully removed by intraoperative transesophageal echocardiography-guided cardiac surgery. Grossly, the surface of the tumor was smooth and translucent. The gelatinous membrane on the surface tore easily, and soft papillary tumor with multiple fronds was visible. Histology confirmed the mass was a papillary fibroelastoma. Postoperative recovery was uneventful. Follow-up transthoracic echocardiogram revealed no residual or recurrence of tumor. The patient was in excellent health at 2-year follow-up. The case is described and the clinical characteristics of cardiac papillary fibroelastoma are reviewed.