Artificial intelligence to enhance prehospital stroke diagnosis and triage: a perspective.

As health systems organize to deliver the highest quality stroke care to their patients, there is increasing emphasis being placed on prehospital stroke recognition, accurate diagnosis, and efficient triage to improve outcomes after stroke. Emergency medical services (EMS) personnel currently rely heavily on dispatch accuracy, stroke screening tools, bypass protocols and prehospital notification to care for patients with suspected stroke, but novel tools including mobile stroke units and telemedicine-enabled ambulances are already changing the landscape of prehospital stroke care. Herein, the authors provide our perspective on the current state of prehospital stroke diagnosis and triage including several of these emerging trends. Then, we provide commentary to highlight potential artificial intelligence (AI) applications to improve stroke detection, improve accurate and timely dispatch, enhance EMS training and performance, and develop novel stroke diagnostic tools for prehospital use.

Prehospital stroke scales outperform National Institutes of Health Stroke Scale in predicting large vessel occlusion in a large academic telestroke network.

INTRODUCTION: Prehospital telestroke evaluations may improve stroke triage compared to paramedic-applied large vessel occlusion scales, but ambulance-based video National Institutes of Health Stroke Scale assessments are challenging. The accuracy of telestroke-administered large vessel occlusion scales has not been investigated, so we sought to evaluate this further. METHODS: This retrospective study included all in-hospital telestroke encounters in a large academic telestroke network from 2019 to 2020. We retrospectively calculated seven large vessel occlusion scales using the in-hospital telestroke National Institutes of Health Stroke Scale (Rapid Arterial oCclusion Evaluation, Cincinnati Stroke Triage Assessment Tool, Field Assessment Stroke Triage for Emergency Destination, 3-Item Stroke Scale, Prehospital Acute Stroke Severity, Vision-Aphasia-Neglect, and Gaze-Face-Arm-Speech-Time). Diagnostic performance was assessed via sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, negative likelihood ratio, and accuracy using established scale thresholds. These results were compared to the National Institutes of Health Stroke Scale at thresholds of 6, 8, and 10. The area under curve was calculated using c-statistics by treating scales as continuous variables. RESULTS: A total of 625 patients were included; 111 (17.8%) patients had an anterior large vessel occlusion, 118 (18.9%) patients had any large vessel occlusion, and 182 (29.1%) patients had stroke mimic diagnosis. The mean age (SD) was 67.9 (15.9), 48.3% were female, and 93.4% were white. The Mean National Institutes of Health Stroke Scale (SD) was 14.9 (8.4) for patients with anterior large vessel occlusion, 4.7 (5.0) for patients with non-large vessel occlusion ischemic stroke, and 4.4 (5.8) for stroke mimic (p < 0.001). Compared to the National Institutes of Health Stroke Scale, Field Assessment Stroke Triage for Emergency Destination, and Rapid Arterial oCclusion Evaluation scales demonstrated higher accuracy and area under curve for large vessel occlusion detection. DISCUSSION: Both the Field Assessment Stroke Triage for Emergency Destination and Rapid Arterial oCclusion Evaluation scales outperformed the National Institutes of Health Stroke Scale for large vessel occlusion detection in patients evaluated by in-hospital telestroke. These scales may be valid alternatives to the National Institutes of Health Stroke Scale examination in this setting.

Emergent use of ticagrelor during endovascular reperfusion in large arterial occlusions.

OBJECTIVE: Given many emerging indications for endovascular interventions in ischemic strokes, a safe and effective adjuvant antiplatelet regimen for acute revascularization has become a subject of interest. Ticagrelor is a direct oral P2Y12 inhibitor that may achieve rapid platelet suppression than standard oral therapies. We report our experience of Ticagrelor use in revascularization of acute large arterial steno-occlusive disease, describing procedural post-procedure thrombotic events, major hemorrhages, and other clinical outcomes. METHODS: This was a single-center retrospective case series of large steno-occlusive disease requiring endovascular reperfusion with emergent adjuvant Ticagrelor, defined as 30 min of the procedure from skin puncture to closure of the arteriotomy. Major outcomes investigated were thromboembolism in the target artery, and symptomatic intracranial or extracranial major hemorrhages. Additional analyses were performed with respect to timing of the administration and use of rescue GPIIb/IIIa inhibitors if any. RESULTS: 73 consecutive patients were identified, presenting with severe ischemic stroke (median NIHSS 16) of large artery origin. 67% required stent placement (45% cervical carotid, 22% intracranial artery), 9.5% angioplasty and 23% mechanical thrombectomy only. Two experienced symptomatic in-stent occlusion, and 7 experienced major hemorrhages (9.5%) including 3 fatal symptomatic intracranial hemorrhages (4.1%). Among 19 subjects (26%) who received pretreatment with Ticagrelor, there were fewer GPIIb/IIIa administration, angioplasty and stenting, without yielding benefit in functional outcome or mortality. GPIIb/IIIa was administered as rescue therapy in 45 subjects (62%), which was found associated with increased bleeding compared to patients receiving Ticagrelor only, in whom no bleeding complications were recorded (16% vs. 0%; p = 0.03). CONCLUSION: We report our findings on Ticagrelor as an adjuvant antiplatelet therapy in ischemic stroke of large arterial origin requiring emergent revascularization. Effectiveness, safety, need for additional rescue treatment, and comparison to other commonly used oral antiplatelets should be investigated in future prospective studies.

Donation after circulatory death: A transplant cardiologist's take on neuroprognostication.

Donation after circulatory death (DCD) is becoming increasingly utilized in heart transplantation and has the potential to further expand the donor pool. As transplant cardiologists gain more familiarity with DCD donor selection, there are many issues that lack consensus including how we incorporate the neurologic examination, how we measure functional warm ischemic time (fWIT), and what fWIT thresholds are acceptable. DCD donor selection calls for prognostication tools to help determine how quickly a donor may expire, and in current practice there is no standardization in how we make these predictions. Current scoring systems help to determine which donor may expire within a specified time window either require the temporary disconnection of ventilatory support or do not incorporate any neurologic examination or imaging. Moreover, the specified time windows differ from other DCD solid organ transplantation without standardization or strong scientific justification for these thresholds. In this perspective, we highlight the challenges faced by transplant cardiologists as they navigate the muddy waters of neuroprognostication in DCD cardiac donation. Given these difficulties, this is also a call to action for the creation of a more standardized approach to improve the DCD donor selection process for appropriate resource allocation and organ utilization.

Disposition and Mass Balance of Etrasimod in Healthy Subjects and In Vitro Determination of the Enzymes Responsible for Its Oxidative Metabolism.

Etrasimod (APD334) is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator (S1P1,4,5 ) in development for treatment of various immune-mediated inflammatory disorders. The disposition and mass balance of a single 2-mg [14 C]etrasimod dose were evaluated in 8 healthy males. An in vitro study was also conducted to identify etrasimod's oxidative metabolizing enzymes. Peak concentrations of etrasimod and total radioactivity in plasma and whole blood were typically reached 4-7 hours postdose. Etrasimod constituted 49.3% of total radioactivity plasma exposure, with multiple minor/trace metabolites making up the remainder. Etrasimod was slowly cleared mainly via biotransformation, predominantly by oxidative metabolism, with unchanged etrasimod recovered in feces accounting for only 11.2% of the dose and none in urine. The mean apparent terminal half-lives of etrasimod and total radioactivity in plasma were 37.8 and 89.0 hours, respectively. Mean cumulative recovery of radioactivity in excreta over 336 hours was 86.9% of the dose, mostly in feces. The prevalent metabolites eliminated in feces were M3 (hydroxy-etrasimod) and M36 (oxy-etrasimod sulfate), accounting for 22.1% and 18.9% of the dose, respectively. From in vitro reaction phenotyping, the predominant enzymes involved in the oxidation of etrasimod were CYP2C8, CYP2C9, and CYP3A4, with minor contributions from CYP2C19 and CYP2J2.

Complex Metabolism of the Novel Neurosteroid, Ganaxolone, in Humans: A Unique Challenge for Metabolites in Safety Testing Assessment.

The human pharmacokinetics, metabolism, and excretion of [14C]-ganaxolone (GNX) were characterized in healthy male subjects (n = 8) following a single 300-mg (150 µCi) oral dose. GNX exhibited a short half-life of 4 hours in plasma, whereas total radioactivity had a half-life of 413 hours indicating extensive metabolism to long-lived metabolites. Identification of the major GNX circulating metabolites required extensive isolation and purification for liquid chromatography-tandem mass spectrometry analysis, together with in vitro studies, NMR spectroscopy, and synthetic chemistry support. This revealed that the major routes of GNX metabolism involved hydroxylation at the 16α-hydroxy position, stereoselective reduction of the 20-ketone to afford the corresponding 20α-hydroxysterol, and sulfation of the 3α-hydroxy group. This latter reaction yielded an unstable tertiary sulfate, which eliminated the elements of H2SO4 to introduce a double bond in the A ring. A combination of these pathways, together with oxidation of the 3ß-methyl substituent to a carboxylic acid and sulfation at the 20α position, led to the major circulating metabolites in plasma, termed M2 and M17. These studies, which led to the complete or partial identification of no less than 59 metabolites of GNX, demonstrated the high complexity of the metabolic fate of this drug in humans and demonstrated that the major circulating products in plasma can result from multiple sequential processes that may not be easily replicated in animals or with animal or human in vitro systems. SIGNIFICANCE STATEMENT: Studies on the metabolism of [14C]-ganaxolone in humans revealed a complex array of products that circulated in plasma, the two major components of which were formed via an unexpected multi-step pathway. Complete structural characterization of these (disproportionate) human metabolites required extensive in vitro studies, along with contemporary mass spectrometry, NMR spectroscopy, and synthetic chemistry efforts, which served to underscore the limitations of traditional animal studies in predicting major circulating metabolites in man.

Telemedicine for Acute Monocular Visual Loss: A Retrospective Large Telestroke Network Experience.

Introduction: Central retinal artery occlusion (CRAO) is an under-recognized stroke subtype that may benefit from hyperacute reperfusion therapies. We aimed to evaluate the ability of telestroke activations to provide CRAO diagnosis and thrombolysis. Methods: This retrospective observational study investigates all encounters conducted for acute visual loss between 2010 and 2021 in our multicentric Mayo Clinic Telestroke Network. Demographics, time from visual loss to telestroke evaluation, ocular examination, diagnostic, and therapeutic recommendations were collected for CRAO subjects. Results: Out of 9,511, 49 encounters (0.51%) were conducted for an acute ocular complaint. Five patients had possible CRAO, and 4 presented within 4.5 h from symptom onset (range 1.5-5 h). None received thrombolytic therapy. All telestroke physicians recommended ophthalmology consultation. Conclusion: Current telestroke assessment of acute visual loss is suboptimal and patients eligible for acute reperfusion therapies may not be offered treatment. Teleophthalmologic evaluations and advanced ophthalmic diagnostic tools should complement telestroke systems.

Telestroke's Role Through the COVID-19 Pandemic and Beyond.

Purpose of review: The goal of this paper is to discuss the role and utilization of telestroke services through the COVID-19 pandemic and to suggest future directions to sustain and increase patients' access to stroke expertise. Recent findings: Telestroke is an innovative and effective tool that has been shown to improve access, quality of care, and outcomes of patients with acute stroke syndromes in resource-limited areas for the last two decades. The COVID-19 pandemic posed a significant challenge and strained healthcare systems worldwide, but it created novel and unique opportunities to expand and increase the utilization of telehealth and telestroke services to deliver personalized healthcare across the continuum of stroke care outside of traditional settings. This rapid and widespread increase in telestroke use was facilitated by the removal of many legislative and regulatory barriers which have limited patients' access to stroke expertise for many years. Summary: As the public health emergency ends, there exists a unique opportunity to optimize and expand upon the pandemic-related rapid growth of telestroke care. Optimal utilization of telehealth and telestroke services will depend on maintaining and improving required infrastructure, laws, and regulations, particularly those governing reimbursement and licensing.

Improving the Telemedicine Evaluation of Patients With Acute Vision Loss: A Call to Eyes.

Acute vision loss related to cerebral or retinal ischemia is a time-sensitive emergency with potential treatment options including IV or intra-arterial thrombolysis and mechanical thrombectomy. However, patients either present in a delayed fashion or present to an emergency department that lacks the subspecialty expertise to recognize and treat these conditions in a timely fashion. Moreover, health care systems in the United States are becoming increasingly reliant on telestroke and teleneurology services for acute neurologic care, making the accurate diagnosis of acute vision loss even more challenging due to critical limitations to the remote video evaluation, including the inability to perform routine ophthalmoscopy. The COVID-19 pandemic has led to a greater reliance on telemedicine services and helped to accelerate the development of novel tools and care pathways to improve remote ophthalmologic evaluation, but these tools have yet to be adapted for use in the remote evaluation of acute vision loss. Permanent vision loss can be disabling for patients, and efforts must be made to increase and improve early diagnosis and management. Herein, the authors outline the importance of improving acute ophthalmologic diagnosis, outline key limitations and barriers to the current video-based teleneurology assessments, highlight opportunities to leverage new tools to enhance the remote assessment of vision loss, and propose new avenues to improve access to emergent ophthalmology subspecialty.

Time in therapeutic range of anticoagulation among patients with atrial fibrillation and cerebral amyloid angiopathy.

Atrial fibrillation (AF) and cerebral amyloid angiopathy (CAA) present risks of ischemic stroke and intracerebral hemorrhage (ICH). Vitamin K antagonist use is associated with fluctuations in international normalized ratio (INR), which predispose to a higher bleeding risk. Patients with a diagnosis of AF and ICH while on a vitamin K antagonist were identified using the Rochester Epidemiology Project. Sixty patients were identified (mean age 81.3 years; 24 men). Thirty-three (55%) exhibited characteristics consistent with possible (n = 25) or probable (n = 8) CAA. Mean time in therapeutic range in the 30 days preceding ICH was 55.4%, with no difference between CAA and non-CAA patients. Mean time spent above therapeutic range (INR > 3.0) was 17.7%, with no difference between CAA and non-CAA patients. Following ICH, 21 (35%) died within 30 days, with total mortality at 76.7% after 176.4 person-years of follow-up (mean 2.9 years). Time in therapeutic range in the 30 days prior to ICH had no significant impact on 7-day mortality, nor risk of recurrent ICH or ischemic stroke. Patients with warfarin-related ICH were often outside of the therapeutic range within the month preceding hemorrhage but more frequently were subtherapeutic. Even with careful avoidance of supratherapeutic INR, vitamin K antagonist use in CAA patients is unlikely to have a major effect in preventing ICH and must be used with caution.

Influence of Platelet Count on Procedure-Related Outcomes After Mechanical Thrombectomy for Large Vessel Occlusion: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare outcomes between patients who underwent mechanical thrombectomy for large vessel occlusion based on platelet count: low versus normal. METHODS: Three studies were included with a pooled cohort of 1125 patients. Data points were collected and pooled by meta-analysis of proportions via a logit transformation to provide a summary statistic. Both fixed-effect and random-effects models were recruited for the analysis. In this meta-analysis, risk of developing symptomatic intracranial hemorrhage, unfavorable clinical outcomes (modified Rankin Scale score >3), and mortality of patients with low platelet counts were compared with patients with normal platelet counts according to the criteria for inclusion used by each study. RESULTS: Of patients, 50 (4.7%) had low platelet count, and 1075 (95.3%) had normal platelet count. Patients in the low platelet count group had a substantially higher risk of mortality (risk ratio 1.93, 95% confidence interval 1.43-2.60, P < 0.0001, I2 = 0%), but no differences in clinical outcomes (risk ratio 0.66, 95% confidence interval 0.40-1.11, P = 0.12, I2 = 0%) or symptomatic intracranial hemorrhage (risk ratio 2.03, 95% confidence interval 0.87-4.70, P = 0.10, I2 = 15%) were noted. CONCLUSIONS: Patients with low platelet counts had increased mortality compared with patients with normal platelet counts following mechanical thrombectomy for large vessel occlusion.

Telemedicine-enabled ambulances and mobile stroke units for prehospital stroke management.

The recognition and management of stroke in the prehospital setting has become increasingly important to improve patient outcomes. Several strategies to advance prehospital stroke care have been developed, including the mobile stroke unit and the telemedicine-enabled ambulance-or "mini-MSU." These strategies both incorporate ambulance-based audio-visual telemedicine evaluation with a vascular neurologist to facilitate faster treatment but differ in several areas including upfront and recurring costs, scalability or growth potential, ability to integrate into existing emergency medical services systems, and interoperability across multiple specialties or conditions. While both the mobile stroke unit and mini-mobile stroke unit model are valid approaches to improve stroke care, the authors aim to compare these models based on costs, scalability, integration, and interoperability in order to guide our prehospital leaders to find the best solutions for their communities.

Acute Epstein-Barr virus infection presenting as Guillain-Barre syndrome.

An 18-year-old man presented with 5-days of a lower extremity rash, sore throat, rapidly progressive bilateral facial numbness and paresthesias in his distal extremities. His neurological examination acutely deteriorated to include moderate bilateral facial weakness in a lower motor neuron pattern, mild flaccid dysarthria, mild bilateral interossei weakness, and diffuse hyporeflexia. In addition to neurological examination, EMG results of acute demyelinating polyradiculoneuropathy were suggestive of Guillain-Barre Syndrome (GBS). Infectious laboratory testing demonstrated acute infection of Epstein-Barr Virus (EBV) with relatively low EBV DNA quantitative values. The patient subsequently developed fever and cervical lymphadenopathy during his hospital course. Contrasting typical GBS, which presents weeks after an acute infection, the patient's presenting symptom of EBV infection was GBS. GBS as a presenting symptom of EBV has not previously been described. This case may represent a unique mechanism for the pathogenesis of GBS in acute infections as opposed to the traditional post-infectious antibody-mediated process.

Vascular Spinal Cord Disorders.

Vascular disorders of the spinal cord are uncommon yet under-recognized causes of myelopathy. Etiologies can be predominantly categorized into clinical and radiographic presentations of arterial ischemia, venous congestion/ischemia, hematomyelia, and extraparenchymal hemorrhage. While vascular myelopathies often produce significant morbidity, recent advances in the understanding and recognition of these disorders should continue to expedite diagnosis and proper management, and ideally improve patient outcomes. This article comprehensively reviews relevant spinal cord vascular anatomy, clinical features, radiographic findings, treatment, and prognosis of vascular disorders of the spinal cord.

Reliability of Field Assessment Stroke Triage for Emergency Destination Scale Use by Paramedics: Mobile Stroke Unit First-Year Experience.

Background and Purpose: Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scale is a helpful tool to triage patients with stroke in the field. However, data on its reliability in the prehospital setting are lacking. We aim to test the reliability of FAST-ED scale when used by paramedics in a mobile stroke unit covering a metropolitan area. Methods: As part of standard operating mobile stroke unit procedures, paramedics initially evaluated patients. If the event characterized a stroke alert, the FAST-ED score was determined by the paramedic upon patient contact (in-person) and then independently by a vascular neurologist (VN) immediately after paramedic evaluation (remotely/telemedicine). This allowed testing of the interrater agreement of the FAST-ED scoring performance between on-site prehospital providers and remotely located VN. Results: Of a total of 238 patients transported in the first 15 months of the mobile stroke unit's activity, 173 were included in this study. Median age was 63 (interquartile range, 55.5­75) years and 52.6% were females. A final diagnosis of ischemic stroke was made in 71 (41%), transient ischemic attack in 26 (15%), intracranial hemorrhage in 15 (9%), whereas 61 (35%) patients were stroke mimics. The FAST-ED scores matched perfectly among paramedics and VN in 97 (56%) instances, while there was 0 to 1-point difference in 158 (91.3%), 0 to 2-point difference in 171 (98.8%), and 3 or more point difference in 2 (1.1%) patients. The intraclass correlation between VN and paramedic FAST-ED scores showed excellent reliability, intraclass correlation coefficient 0.94 (95% CI, 0.92­0.96; P<0.001). When VN recorded FAST-ED score ≥3, paramedics also scored FAST-ED≥3 in majority of instances (63/71 patients; 87.5%). A large vessel occlusion was identified in 16 (9.2%) patients; 13 occlusions were identified with a FAST-ED≥3 while 3 were missed. All of the latter patients had National Institutes of Health Stroke Scale score ≤5. Conclusions: We demonstrate excellent reliability of FAST-ED scale performed by paramedics when compared with VN, indicating that it can be accurately performed by paramedics in the prehospital setting.

Safety of Ticagrelor in Moderate and Severe Acute Ischemic Stroke: A Single-Center Retrospective Review.

OBJECTIVES: Ticagrelor may be superior to aspirin after minor ischemic stroke or TIA, particularly in patients with symptomatic atherosclerotic disease. However, there may be an increased risk of intracerebral hemorrhage in patients with moderate to severe ischemic stroke, and ticagrelor has not been studied in this patient population. Therefore, we sought to evaluate the safety of ticagrelor after moderate or severe ischemic stroke. MATERIALS AND METHODS: Retrospective chart review of all patients admitted with acute ischemic stroke and NIHSS 6 or greater who were discharged on ticagrelor between January 2016 and December 2019. Patients who underwent angioplasty, stenting or carotid revascularization during the hospitalization were excluded. RESULTS: Of 183 patients discharged on ticagrelor, 61 patients were included. Median age was 61 (IQR 52-68); 33 (54%) patients were men. Median NIHSS was 11 (IQR 8-15). Fourteen (23%) patients received IV alteplase and 35 (57%) patients received mechanical thrombectomy. Stroke mechanism was large artery atherosclerosis in 53 (87%) of patients, of which 40 (71%) were deemed intracranial atherosclerosis. Final infarct volume was greater than 10 mL in 32 (52%) patients. Follow-up information was available for 53 (87%) patients; median length of follow-up was 3 (IQR 2-6) months. Six (10%) patients experienced recurrent ischemic stroke. No patients experienced symptomatic intracerebral hemorrhage after initiation of ticagrelor. One (2%) patient experienced major bleeding. CONCLUSIONS: This study provides preliminary evidence supporting the potential safety of ticagrelor following moderate or severe acute ischemic stroke. These findings support the need for future prospective studies.

Neurologic complications of diseases of the aorta.

Neurologic complications of diseases of the aorta are common, as the brain and spinal cord function is highly dependent on the aorta and its branches for blood supply. Any disease impacting the aorta may have significant impact on the ability to deliver oxygenated blood to the central nervous system, resulting in ischemia-and if prolonged-cerebral and spinal infarct. The breadth of pathology affecting the aorta is diverse and neurologic complications can vary dramatically based on the location, severity, and underlying etiology. This chapter outlines the major pathology of the aorta while highlighting the associated neurologic complications. This chapter covers the entire spectrum of neurologic complications associated with aortic disease by beginning with a detailed overview of the spinal cord vascular anatomy followed by a discussion of the most common aortic pathologies affecting the nervous system, including aortic aneurysm, aortic dissection, aortic atherosclerosis, inflammatory and infectious aortopathies, congenital abnormalities, and aortic surgery.

Stroke Thrombolysis in Patients Taking Ticagrelor -Two Successful Cases and a Review of the Literature.

BACKGROUND: Ticagrelor is a novel antiplatelet agent that is frequently used for secondary prevention in coronary artery disease and has emerging evidence in stroke after the recent results of SOCRATES and THALES trials. The use of intravenous thrombolysis with alteplase in acute ischemic stroke (AIS) patients on ticagrelor is a topic of debate as the safety profile of ticagrelor in this setting is not well established. METHODS: We identified consecutive AIS patients taking ticagrelor who received intravenous alteplase at a comprehensive stroke center from January 2016 to December 2019. We then performed a literature search to capture all known published cases of intravenous thrombolysis in stroke patients on ticagrelor. RESULTS: Of the 3896 patients who were treated for AIS at our local comprehensive stroke center during this time period, two patients received intravenous alteplase while on ticagrelor. Both patients had posterior circulation acute strokes and were successfully treated with intravenous alteplase without a systemic or intracranial bleeding event. Only five other cases of intravenous thrombolysis in AIS patients on ticagrelor have been reported in the literature. Among these cases, four of the five cases had a hemorrhagic complication. CONCLUSION: Despite prior reports of hemorrhagic complications with use of IV alteplase in setting of pre-treatment with ticagrelor, we report the safe use of intravenous thrombolysis in two cases presenting with acute ischemic stroke. Until safety is established in large studies, decision for thrombolysis should be made on case-by-case basis.

Utility of HAS-BLED and CHA2DS2-VASc Scores Among Patients With Atrial Fibrillation and Imaging Evidence of Cerebral Amyloid Angiopathy.

OBJECTIVE: To determine the utility of the HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly, Drugs/alcohol concomitantly) and CHA2DS2-VASc (Congestive heart failure, Hypertension, Age, Diabetes, previous Stroke/transient ischemic attack-VAScular disease) scores among patients on anticoagulation (AC) therapy for atrial fibrillation (AF) who have evidence of cerebral amyloid angiopathy (CAA). PATIENTS AND METHODS: Patients older than 55 years with a diagnosis of AF who had a nontraumatic intracerebral hemorrhage (ICH) while on AC therapy between 1995 and 2016 were identified using the Rochester Epidemiology Project Database. Medical records were reviewed, including imaging of the brain, to identify baseline characteristics, AC use, and outcomes. RESULTS: A total of 65 patients were identified (mean age, 81.3 years); 35 (53.8%) had evidence of possible/probable CAA. Mean HAS-BLED score in the CAA group was significantly lower (2.1) than that of the non-CAA group (2.9; P<.001). Mortality after ICH, adjusted for HAS-BLED scores, was not significantly different among patients with and without CAA. Sixteen patients restarted on AC therapy after ICH; CHA2DS2-VASc scores were no different between this group and those who were not restarted. Among patients with CAA, the overall rate of ICH recurrence was 8.6% over 93.5 person-years of follow-up. Among patients with CAA, the rate of ICH recurrence was 3.2 per 100 patient-years, higher than their HAS-BLED scores would predict (1.9 bleeds/100 patient-years). CONCLUSION: HAS-BLED scores were lower in patients who had evidence of CAA compared with those without, suggesting underestimation of ICH risk in patients with CAA. CHA2DS2-VASc scores did not affect resumption of AC therapy. ICH recurrence was higher in patients with CAA than their HAS-BLED scores predicted. Current risk assessment scoring systems do not accurately account for CAA in patients with AF on AC.

High Mortality Rates Among Patients With Non-Traumatic Intracerebral Hemorrhage and Atrial Fibrillation on Antithrombotic Therapy Are Independent of the Presence of Cerebral Amyloid Angiopathy: Insights From a Population-Based Study.

Background Intracerebral hemorrhage (ICH) risk is higher in elderly patients with atrial fibrillation on antithrombotic therapy as well as those with cerebral amyloid angiopathy (CAA). We investigated if mortality among patients with atrial fibrillation on antithrombotic therapy presenting with non-traumatic ICH was influenced by underlying CAA. Methods and Results We used the Rochester Epidemiology Project to identify 6045 patients with atrial fibrillation aged >55 years on anticoagulation or antiplatelet therapy from 1995 to 2016. Seventy-four patients in this cohort presented with non-traumatic ICH. Medical records including imaging data were reviewed to identify those with CAA and record baseline variables and outcomes of interest; 38 of our 74 patients (51.4%) (mean age 81.5 years) met Modified Boston Criteria for possible or probable CAA. Twenty-six of 74 patients (35%) died during the first 30 days while 56 of the 74 (76%) patients died by 10 years follow-up after index ICH. Overall mortality was not significantly different between the CAA and non-CAA groups at any point of time during follow-up (P=0.89) even amongst patients restarted on anticoagulation +/- antiplatelet (n=19) (P=0.46) or those patients restarted only on antiplatelet therapy (n=22) (P=0.66). Three of the 41 patients who restarted on antithrombotic therapy had a recurrent ICH; these 3 patients met criteria for possible or probable CAA. Conclusions Although more than half of our patients with atrial fibrillation on antithrombotic therapy and non-traumatic ICH met Modified Boston Criteria for CAA, CAA did not significantly influence the high mortality seen in this cohort.