Objective: Mindfulness training can relieve posttraumatic stress disorder (PTSD) symptoms in military veterans and others but is inconsistently accessible. Self-guided mobile apps could improve access but their acceptability, feasibility, and benefits for veterans with PTSD have not been established. We conducted a pilot randomized trial of Mindfulness Coach (MC), a free, publicly available, trauma-informed mobile app tailored to veterans. Method: U.S. veterans with PTSD (n = 173) were randomized to self-guided use of MC or waitlist control (WLC) with 8-week follow-up. Clinical outcomes were PTSD symptoms (PTSD Symptom Checklist-5), depression symptoms (Patient Health Questionnaire, nine item), and psychosocial functioning (Brief Inventory of Psychosocial Functioning). Primary analyses were intent-to-treat using linear mixed models with maximum likelihood estimation. App uptake, objective usage, and usability ratings measured acceptance and feasibility. Results: Participants varied in age, gender, and ethnoracial identity; most reported recent mental health care utilization. Although study attrition was high (68.4% overall) due to participant dropout (treatment: 43.0%; control: 43.7%) and technical study issues (23% overall), diagnostic tests showed no evidence of bias due to missingness. Study completers (MC: n = 19; WLC: n = 37) showed medium effects on PTSD symptoms (b = -9.31, d = -0.69) and depression (b = -3.10, d = -0.52). Higher-intensity users showed greater benefits. App engagement trended lower for women and minoritized subpopulations. No changes were observed in psychosocial functioning. Usability and helpfulness ratings were favorable. Conclusions: Transdiagnostic clinical benefits indicate promise for MC as a public health resource for veterans with PTSD. Further study is warranted to confirm these benefits and ensure consistent engagement across subpopulations.

Colonoscopy is accurate but inefficient for colorectal cancer (CRC) prevention due to the low (~7-8%) prevalence of target lesions, advanced adenomas. We leveraged rectal mucosa to identify patients who harbor CRC field carcinogenesis by evaluating chromatin 3D architecture. Supranucleosomal disordered chromatin chains (~5-20 nm, ~1 kbp) fold into chromatin packing domains (~100-200 nm, ~100-1,000 kbp). In turn, the fractal-like conformation of DNA within chromatin domains and the folding of the genome into packing domains has been shown to influence multiple facets of gene transcription, including the transcriptional plasticity of cancer cells. We deployed an optical spectroscopic nanosensing technique, chromatin-sensitive partial wave spectroscopic microscopy (csPWS), to evaluate the packing density scaling D of the chromatin chain conformation within packing domains from rectal mucosa in 256 patients with varying degrees of progression to colorectal cancer. We found average packing scaling D of chromatin domains was elevated in tumor cells, histologically normal-appearing cells 4 cm proximal to the tumor, and histologically normal-appearing rectal mucosa compared to cells from control patients (p<0.001). Nuclear D had a robust correlation with the model of 5-year risk of CRC with r2=0.94. Furthermore, rectal D was evaluated as a screening biomarker for patients with advanced adenomas presenting an AUC of 0.85 and 85% sensitivity and specificity. Artificial Intelligence (AI)-enhanced csPWS improved diagnostic performance with AUC=0.90. Considering the low sensitivity of existing CRC tests, including liquid biopsies, to early-stage cancers our work highlights the potential of chromatin biomarkers of field carcinogenesis in detecting early, significant precancerous colon lesions.

As leaders, cardiothoracic surgeons must learn about and undergo transitions during the stages of a successful career. The authors discuss the process of transitions and the roles of networks to support professional transitions. The role of engagement in surgical organizations to create these networks and help support professional transitions is also explored. Finally, the authors describe how our engagement in surgical organizations can successfully impact our specialty of cardiothoracic surgery.

The proper regulation of muscle stem cell (MuSC) fate by cues from the niche is essential for regeneration of skeletal muscle. How pro-regenerative niche factors control the dynamics of MuSC fate decisions remains unknown due to limitations of population-level endpoint assays. To address this knowledge gap, we developed a dual fluorescence imaging time lapse (Dual-FLIT) microscopy approach that leverages machine learning classification strategies to track single cell fate decisions with high temporal resolution. Using two fluorescent reporters that read out maintenance of stemness and myogenic commitment, we constructed detailed lineage trees for individual MuSCs and their progeny, classifying each division event as symmetric self-renewing, asymmetric, or symmetric committed. Our analysis reveals that treatment with the lipid metabolite, prostaglandin E2 (PGE2), accelerates the rate of MuSC proliferation over time, while biasing division events toward symmetric self-renewal. In contrast, the IL6 family member, Oncostatin M (OSM), decreases the proliferation rate after the first generation, while blocking myogenic commitment. These insights into the dynamics of MuSC regulation by niche cues were uniquely enabled by our Dual-FLIT approach. We anticipate that similar binary live cell readouts derived from Dual-FLIT will markedly expand our understanding of how niche factors control tissue regeneration in real time.

Background Posttraumatic stress disorder (PTSD) among US military veterans can adversely impact their concerned significant others (CSOs; eg, family members and romantic partners). Mobile apps can be tailored to support CSO mental health through psychoeducation, coping skills, and stress monitoring. Objective This study assessed the feasibility, acceptability, and potential efficacy of PTSD Family Coach 1.0, a free, publicly available app that includes psychoeducation, stress management tools, self-assessments, and features for connecting to alternative supports, compared with a psychoeducation-only version of the app for cohabitating CSOs of veterans with PTSD. Methods A total of 200 participants with an average age of 39 (SD 8.44) years, primarily female (193/200, 97%), and White (160/200, 80%) were randomized to self-guided use of either PTSD Family Coach 1.0 (n=104) or a psychoeducation-only app (n=96) for 4 weeks. Caregiver burden, stress, depression, anxiety, beliefs about treatment, CSO self-efficacy, and relationship functioning assessed using measures of dyadic adjustment, social constraints, and communication danger signs were administered via a web survey at baseline and after treatment. User satisfaction and app helpfulness were assessed after treatment. Data were analyzed using linear mixed methods. Results Overall, 50.5% (101/200) of randomized participants used their allocated app. Participants found PTSD Family Coach 1.0 somewhat satisfying (mean 4.88, SD 1.11) and moderately helpful (mean 2.99, SD 0.97) to use. Linear mixed effects models revealed no significant differences in outcomes by condition for caregiver burden (P=.45; Cohen d=0.1, 95% CI −0.2 to 0.4), stress (P=.64; Cohen d=0.1, 95% CI −0.4 to 0.6), depression (P=.93; Cohen d= 0.0, 95% CI −0.3 to 0.3), anxiety (P=.55; Cohen d=−0.1, 95% CI −0.4 to 0.2), beliefs about treatment (P=.71; Cohen d=0.1, 95% CI −0.2 to 0.3), partner self-efficacy (P=.59; Cohen d=−0.1, 95% CI −0.4 to 0.2), dyadic adjustment (P=.08; Cohen d=−0.2, 95% CI −0.5 to 0.0), social constraints (P=.05; Cohen d=0.3, 95% CI 0.0-0.6), or communication danger signs (P=.90; Cohen d=−0.0, 95% CI −0.3 to 0.3). Post hoc analyses collapsing across conditions revealed a significant between-group effect on stress for app users versus nonusers (β=−3.62; t281=−2.27; P=.02). Conclusions Approximately half of the randomized participants never used their allocated app, and participants in the PTSD Family Coach 1.0 condition only opened the app approximately 4 times over 4 weeks, suggesting limitations to this app version’s feasibility. PTSD Family Coach 1.0 users reported moderately favorable impressions of the app, suggesting preliminary acceptability. Regarding efficacy, no significant difference was found between PTSD Family Coach 1.0 users and psychoeducation app users across any outcome of interest. Post hoc analyses suggested that app use regardless of treatment condition was associated with reduced stress. Further research that improves app feasibility and establishes efficacy in targeting the domains most relevant to CSOs is warranted. Trial Registration ClinicalTrials.gov NCT02486705; https://clinicaltrials.gov/ct2/show/NCT02486705

Posttraumatic stress disorder (PTSD) among U.S. military veterans can adversely impact their concerned significant others (CSOs; e.g., family, romantic partners). Mobile apps can be tailored to support CSO mental health with psychoeducation, coping skills, and stress monitoring. The present study assessed the feasibility, acceptability, and potential efficacy of PTSD Family Coach 1.0, a free, publicly available app for CSOs of veterans with PTSD. Two hundred participants who were an average of 39 years old (SD = 8.44), primarily female (97%), and White (80%) were randomized to self-guided use of either PTSD Family Coach 1.0 (n = 104) or a psychoeducation-only app (n = 96) for four weeks. Caregiver burden, stress, depression, anxiety, beliefs about treatment, and relationship functioning were assessed via web survey at baseline and posttreatment. User satisfaction and app helpfulness were assessed at posttreatment. 101 (50.5%) randomized participants used their allocated app. Participants found PTSD Family Coach 1.0 somewhat satisfying to use (M=4.88, SD=1.11) and moderately helpful (M=2.99, SD=0.97). Linear mixed effects models revealed no significant differences in outcomes by condition. Post hoc analyses collapsing across conditions revealed a significant between-groups effect on stress for app users versus nonusers (beta = -3.62, t(281)=-2.27, P=.023). Although participants found PTSD Family Coach 1.0 acceptable, suboptimal app use suggests limitations to this version’s feasibility. App use regardless of condition was associated with reduced stress.

Many veterans receive behavioral health care services from providers in their communities. The Community Provider Toolkit (the Toolkit) is a website developed by the National Center for PTSD and the Department of Veterans Affairs intended to provide community mental health care providers with key veteran-focused educational resources. This mixed-methods study examined the potential impact of the Toolkit on provider knowledge and behaviors. Sixty-four clinicians in the community who currently or plan to provide services to veterans were surveyed. The majority of providers found the website useful and easy to navigate. After visiting the site, many providers found additional online and educational resources that they would add to a hypothetical treatment plan. Forty-five providers completed a 1-month follow-up survey focused on use of the Toolkit. Results indicate that the Toolkit may be a valuable tool for increasing provider knowledge about veteran-specific resources.

A profound characteristic of field cancerization is alterations in chromatin packing. This study aimed to quantify these alterations using electron microscopy image analysis of buccal mucosa cells of laryngeal, esophageal, and lung cancer patients. Analysis was done on normal-appearing mucosa, believed to be within the cancerization field, and not tumor itself. Large-scale electron microscopy (nanotomy) images were acquired of cancer patients and controls. Within the nuclei, the chromatin packing of euchromatin and heterochromatin was characterized. Furthermore, the chromatin organization was quantified through chromatin packing density scaling. A significant difference was found between the cancer and control groups in the chromatin packing density scaling parameter for length scales below the optical diffraction limit (200 nm) in both the euchromatin (p = 0.002) and the heterochromatin (p = 0.006). The chromatin packing scaling analysis also indicated that the chromatin organization of cancer patients deviated significantly from the control group. They might allow for novel strategies for cancer risk stratification and diagnosis with high sensitivity. This could aid clinicians in personalizing screening strategies for high-risk patients and follow-up strategies for treated cancer patients.

Introduction: Intravenous alteplase improves functional outcome in patients with acute ischemic stroke. While patients often have better outcomes, other patients may experience recurrent or worsening symptoms. We sought to determine the association between stroke subtype and neurologic deterioration in this study cohort. Methods: Data were abstracted from a prospective quality improvement registry at a comprehensive stroke center. Patients with symptomatic intracranial hemorrhage, no follow-up imaging, code status change to comfort measures only in the first 24 hours, or stroke mimics were excluded. Recurrent cerebrovascular events (RCVE) were defined as any new or worsening symptoms due to cerebral ischemia in the absence of intracranial hemorrhage or an alternative etiology such as infection or seizure. We compared demographic factors, vascular comorbidities, admission blood pressure, medications, use and timing of antithrombotics during hospitalization, admission NIH stroke scale, endovascular intervention, stroke subtype [Cardioembolic, large artery atherosclerosis, small vessel disease, cryptogenic, and other defined (such as dissection, hypercoagulability, cancer related, illicit drug use)], and good 90-day outcome (mRS 0-1) between the two groups using Fisher’s exact test and t-test as indicated. We then performed multivariable logistic regression analyses to determine associations between stroke subtypes and RCVE. Results: We identified 705 patients treated with tPA, and 606 met the inclusion criteria. The rate of RCVE was 5.8% (35/606). In multivariable analyses, when compared to cardioembolic/cryptogenic stroke, RCVE was more common in small vessel disease (adjusted OR 9.51 p=0.029), large vessel disease (adjusted OR 5.60, p=0.033), and other stroke mechanisms (adjusted OR 11.29, p=0.019). RCVE was associated with more disability at 90 days when compared to non-RCVE (median mRS 4, IQR 3 vs. median mRS 3, IQR 2, p = 0.016). Conclusions: Non-cryptogenic/Non-cardioembolic stroke subtypes are associated with early RCVE, and RCVE is associated with long term disability. Studies are needed to confirm our findings and test interventions optimizing stroke prevention strategies in these subtypes.

Background: Symptomatic vertebrobasilar (VB) atherosclerotic disease is associated with a high risk of recurrent stroke despite optimal medical therapy. Objective: In this study, we aim to examine the prognosis and associations between risk factors and recurrent major cardiovascular events (MACE) in patients with symptomatic VB stenosis randomized in the medical arm of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study. Methods: Data from subjects in the medical arm of the SAMMPRIS trial with an infarct in the territory of vertebral or basilar arteries (n= 73) were analyzed. The primary outcome was MACE: defined as stroke, myocardial infarction, or other cardiovascular death during follow up. Mean risk factor values were compared between subjects who met the primary outcome at 2 years versus those who did not, using T-tests and χ2 tests. Results: Among 73 patients with VB stenosis randomized to medical treatment, 18 patients (24.6%) had recurrent MACE over a mean follow up of 2.8 years. This was significantly less than the rate of MACE in those with VB enrolled in the WASID trial (9.7 per 100-patient years vs. 20.9 per 100-patient years, p<0.01). Predictors of MACE at 2 years were increased triglyceride level (adjusted OR per 50 units increase in triglyceride 1.94, 95% CI 1.15-3.28) and increased HbA1c level (adjusted OR per 1 unit increase in HbA1c 2.07, 95% CI 0.97-4.45), and lower physical activity status measured by PACE (out of target defined by PACE ≤ 4: moderate activity < 5 days per week or intense activity < 3 days per week) (2.5 ± 1.0 vs. 3.3 ± 1.8, p = 0.028) (Table). Conclusions: In patients with symptomatic VB disease, improvement of medical treatment over time led to a reduction in cardiovascular event rates but this risk remains elevated as nearly 1 in 5 patients had MACE within 2 years. Further risk factor optimization and lifestyle changes are needed to reduce the rates of MACE in this patient population.

BACKGROUND:There is limited data on predictors of symptomatic intracranial haemorrhage (sICH) in patients who underwent mechanical thrombectomy. In this study, we aim to determine those predictors with external validation.METHODS:We evaluated mechanical thrombectomy in a derivation cohort of patients at a comprehensive stroke centre over a 30-month period. Clinical and radiographic data on these patients were obtained from the prospective quality improvement database. sICH was defined using the European Cooperative Acute Stroke Study III. We compared clinical and radiographic characteristics between patients with and without sICH using χ2 and t tests to identify independent predictors of sICH with p<0.1. Significant variables were then combined in a multivariate logistic regression model to derive an sICH prediction score. This score was then validated using data from the Blood Pressure After Endovascular Treatment multicentre prospective registry.RESULTS:We identified 578 patients with acute ischaemic stroke who received thrombectomy, 19 had sICH (3.3%). Predictive factors of sICH were: thrombolysis in cerebral ischaemia (TICI) score, Alberta stroke program early CT score (ASPECTS), and glucose level, and from these predictors, we derived the weighted TICI-ASPECTS-glucose (TAG) score, which was associated with sICH in the derivation (OR per unit increase 1.98, 95% CI 1.48 to 2.66, p<0.001, area under curve ((AUC)=0.79) and validation (OR per unit increase 1.48, 95% CI 1.22 to 1.79, p<0.001, AUC=0.69) cohorts.CONCLUSION:High TAG scores are associated with sICH in patients receiving mechanical thrombectomy. Larger studies are needed to validate this scoring system and test strategies to reduce sICH risk and make thrombectomy safer in patients with elevated TAG scores.

HomeCirculation: Arrhythmia and ElectrophysiologyVol. 13, No. 2Left Atrial Appendage Morphology Improves Prediction of Stagnant Flow and Stroke Risk in Atrial Fibrillation Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessLetterPDF/EPUBLeft Atrial Appendage Morphology Improves Prediction of Stagnant Flow and Stroke Risk in Atrial Fibrillation Shadi Yaghi, MD, Andrew Chang, MS, Gian Ignacio, BS, Erica Scher, MPH, Nikhil Panda, MD, Antony Chu, MD, Michael Wu, MD, Aaron Lord, MD, Brian Mac Grory, MD, Karen Furie, MD, Mitchell S.V. Elkind, MD, Michael Atalay, MD and Christopher Song, MD Shadi YaghiShadi Yaghi Correspondence to: Shadi Yaghi, MD, New York Langone Hospital, 150 55th St, Brooklyn, NY 11220. Email E-mail Address: [email protected] Department of Neurology, New York Langone Hospital, Brooklyn (S.Y., E.S., A.L.). , Andrew ChangAndrew Chang Department of Neurology (A. Chang, G.I., B.M.G., K.F.), The Warren Alpert Medical School of Brown University, Providence, RI. , Gian IgnacioGian Ignacio Department of Neurology (A. Chang, G.I., B.M.G., K.F.), The Warren Alpert Medical School of Brown University, Providence, RI. , Erica ScherErica Scher Department of Neurology, New York Langone Hospital, Brooklyn (S.Y., E.S., A.L.). , Nikhil PandaNikhil Panda Division of Cardiovascular Medicine, Department of Internal Medicine (N.P., A. Chu, M.W., C.S.), The Warren Alpert Medical School of Brown University, Providence, RI. , Antony ChuAntony Chu Division of Cardiovascular Medicine, Department of Internal Medicine (N.P., A. Chu, M.W., C.S.), The Warren Alpert Medical School of Brown University, Providence, RI. , Michael WuMichael Wu Division of Cardiovascular Medicine, Department of Internal Medicine (N.P., A. Chu, M.W., C.S.), The Warren Alpert Medical School of Brown University, Providence, RI. , Aaron LordAaron Lord Department of Neurology, New York Langone Hospital, Brooklyn (S.Y., E.S., A.L.). , Brian Mac GroryBrian Mac Grory Department of Neurology (A. Chang, G.I., B.M.G., K.F.), The Warren Alpert Medical School of Brown University, Providence, RI. , Karen FurieKaren Furie Department of Neurology (A. Chang, G.I., B.M.G., K.F.), The Warren Alpert Medical School of Brown University, Providence, RI. , Mitchell S.V. ElkindMitchell S.V. Elkind Department of Neurology, College of Physicians and Surgeons (M.S.V.E.) Department of Epidemiology, Mailman School of Public Health, Columbia University (M.S.V.E.). , Michael AtalayMichael Atalay Department of Radiology (M.A.), The Warren Alpert Medical School of Brown University, Providence, RI. and Christopher SongChristopher Song Division of Cardiovascular Medicine, Department of Internal Medicine (N.P., A. Chu, M.W., C.S.), The Warren Alpert Medical School of Brown University, Providence, RI. Originally published27 Jan 2020https://doi.org/10.1161/CIRCEP.119.008074Circulation: Arrhythmia and Electrophysiology. 2020;13:e008074Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 27, 2020: Ahead of Print The left atrial appendage (LAA) is the most common site of thrombus formation in patients with atrial fibrillation (AF).1 Therefore, better knowledge of the morphology, physiology, and function of the LAA may provide a better estimate of stroke risk.The LAA morphology is currently classified into 4 categories: chicken-wing, windsock, cauliflower, and cactus. Chicken-wing is the most common and carries lower risk.2,3 This classification system, however, lacks consistent inter-rater reliability and correlation with stroke risk.Previously, we hypothesized that the angle of the bend in the LAA may be a more important correlate of stroke risk than the traditionally described morphology.4 We proposed a simple classification system of LAA morphology, with low risk (LAA-L) defined as one lobe with an acute angle (<90°) bend arising from the proximal or middle portion and high risk (high-risk morphology [LAA-H]) defined as all other morphologies (Figure). This was superior to the current system using the chicken-wing morphology in correlating with cardioembolic stroke.4Download figureDownload PowerPointFigure. The figure shows 4 chicken-wing morphologies. The upper 2 have nonacute angles and were classified as high-risk morphology, whereas the lower 2 have acute angles and were classified as low-risk morphology.We aimed to determine the association between LAA morphology (using both classification systems), LAA–flow velocity, and stroke prevalence in patients with AF undergoing ablation.Patient PopulationWe obtained Institutional Review Board approval to retrospectively review medical records of consecutive patients with AF selected for ablation over 4 years who underwent a cardiac computed tomography angiography and transesophageal echocardiogram. Data is available upon request to corresponding author.Predictors and OutcomesThe primary predictors, in separate analyses, were LAA-H and nonchicken-wing LAA morphology. We previously reported very good inter-rater agreement with LAA morphology adjudication between 2 reviewers (Drs Yaghi and Atalay).4The primary end point was the composite of history of stroke, history of transient ischemic attack, or covert nonlacunar brain infarct on brain imaging. The secondary end point was reduced LAA–flow velocity (≤20 cm/s).5Statistical AnalysisWe compared the primary and secondary end point rates across the different LAA morphologies using Fisher test or nonparametric tests. Adjusting for CHADS2-Vasc score (excluding history of stroke or transient ischemic attack as it is included in the study outcome), multivariable models were used to determine associations between LAA morphology and these end points.We identified 408 patients with AF selected for ablation; 379 patients underwent cardiac computed tomography angiography, and 298 underwent transesophageal echocardiogram; 83 patients had a brain computed tomography or magnetic resonance imaging performed for review. The interval (in years) between brain imaging and chart review between those with or without cortical infarcts was not significantly different (1.25 [1.40] versus 2.13 [2.14], P=0.152). The mean age in years was 62.5±10.3, and 73.5% (300/408) were men. The primary end point occurred in 32 patients (7.8%), and the secondary end point LAA–flow velocity (≤20 cm/s) occurred in 6.4% (19/298). Furthermore, 45% (58/129) of patients with CHADS2-Vasc 0 to 1 (low risk) had a high-risk LAA morphology (LAA-H).Univariate AnalysesIn univariate analyses, patients who met the primary outcome had increased prevalence of nonchicken-wing morphology (67.7% [21/31] versus 44.2% [154/348], P=0.014) and LAA-H morphology (80.6% [25/31] versus 51.7% [180/348], P=0.002). In addition, there was increased prevalence of reduced LAA–flow velocity (≤20 cm/s) in patients with LAA-H (78.9% [15/19] versus 50.9% [142/279], P=0.019), but this did not reach significance with nonchicken-wing morphology (68.4% [13/19] versus 43.4% [121/279], P=0.054).The rates of primary outcome were similar between patients with nonchicken-wing/LAA-H (12.0%) and chicken-wing/LAA-H (13.3%) and higher than that of chicken-wing/LAA-L (3.4%; P=0.005). In addition, the prevalence of reduced LAA–flow velocity (≤20 cm/s) were similar in patients with nonchicken-wing/LAA-H (9.7%) and chicken-wing/LAA-H (8.7%) and higher than that of chicken-wing/LAA-L (2.8%; P=0.049).Multivariable ModelsOn multivariable analyses adjusting for CHADS2-Vasc score, LAA-H (adjusted odds ratio, 3.63 [95% CI, 1.44–9.14]) and nonchicken-wing LAA morphology (adjusted odds ratio, 2.52 [95% CI, 1.15–5.53]) were associated with the primary end point. These associations were present in men (odds ratio, 2.89; P=0.047) and women (odds ratio, 7.18; P=0.068).In this study, we show that the LAA appendage morphology can predict stagnant blood flow and stroke rates in patients with AF. In addition, the LAA-H/L classification system we proposed may provide a better estimate of stroke risk and flow dynamics in the LAA than the current classification system, suggesting that the angle of the bend in the LAA may be a more important correlate of stroke risk than the traditionally described morphology.The association between LAA morphology and stroke risk could be a tool to improve risk stratification when added to current stratification scores such as the CHADS2-Vasc. For instance, patients with AF considered low risk by clinical scores but with LAA-H may be a subgroup where anticoagulation can be tested in clinical trials.Our study is limited by being small-sampled single-center retrospective and, therefore, larger multicenter studies are needed to confirm our findings and to determine whether LAA morphology is useful when added to other cardiac biomarkers to estimate stroke risk and response to anticoagulation therapy.Nonstandard Abbreviations and AcronymsAFatrial fibrillationLAAleft atrial appendageLAA-Hhigh-risk morphologyLAA-Llow-risk morphologySources of FundingThis study was funded by the American Heart Association grant 17MCPRP33670965.DisclosuresNone.FootnotesFor Sources of Funding and Disclosures, see page 171.Correspondence to: Shadi Yaghi, MD, New York Langone Hospital, 150 55th St, Brooklyn, NY 11220. Email [email protected]comReferences1. Yaghi S, Song C, Gray WA, Furie KL, Elkind MS, Kamel H. Left atrial appendage function and stroke risk.Stroke. 2015; 46:3554–3559. doi: 10.1161/STROKEAHA.115.011273LinkGoogle Scholar2. Di Biase L, Santangeli P, Anselmino M, Mohanty P, Salvetti I, Gili S, Horton R, Sanchez JE, Bai R, Mohanty S, et al. Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation? Results from a multicenter study.J Am Coll Cardiol. 2012; 60:531–538. doi: 10.1016/j.jacc.2012.04.032CrossrefMedlineGoogle Scholar3. Yaghi S, Chang AD, Hung P, Mac Grory B, Collins S, Gupta A, Reynolds J, Finn CB, Hemendinger M, Cutting SM, et al. Left atrial appendage morphology and embolic stroke of undetermined source: a Cross-Sectional Multicenter Pilot Study.J Stroke Cerebrovasc Dis. 2018; 27:1497–1501. doi: 10.1016/j.jstrokecerebrovasdis.2017.12.036CrossrefMedlineGoogle Scholar4. Yaghi S, Chang AD, Akiki R, Collins S, Novack T, Hemendinger M, Schomer A, Grory BM, Cutting S, Burton T, et al. The left atrial appendage morphology is associated with embolic stroke subtypes using a simple classification system: A proof of concept study.J Cardiovasc Comput Tomogr. 2019; pii: S1934–5925(19)30071-1. doi: 10.1016/j.jcct.2019.04.005CrossrefGoogle Scholar5. Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography.Ann Intern Med. 1998; 128:639–647. doi: 10.7326/0003-4819-128-8-199804150-00005CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Soni S, Duggal B, Upadhyay J, Basu-Ray I, Kumar N and Singh Bhadoria A (2023) "Does left atrial appendage morphology and dimension differ amongst etiological stroke subtypes in patients without known Atrial Fibrillation? Results from the Left Atrial Appendage morphology and dimension assessment by TEE in patients with stroke without known Atrial Fibrillation (LAMDA-STROKE) Study.", Indian Heart Journal, 10.1016/j.ihj.2023.03.001, Online publication date: 1-Mar-2023. Ward R and Deshmukh A (2022) Cardiac magnetic resonance imaging is a promising modality for left atrial appendage occlusion planning, Journal of Cardiovascular Electrophysiology, 10.1111/jce.15721, 33:12, (2651-2652), Online publication date: 1-Dec-2022. Fang R, Wang Z, Zhao X, Wang J, Li Y, Zhang Y, Chen Q, Wang J, Liu Q, Chen M and Li Z (2022) Stroke risk evaluation for patients with atrial fibrillation: Insights from left atrial appendage with fluid-structure interaction analysis, Computers in Biology and Medicine, 10.1016/j.compbiomed.2022.105897, 148, (105897), Online publication date: 1-Sep-2022. Fang R, Li Y, Wang J, Wang Z, Allen J, Ching C, Zhong L and Li Z (2022) Stroke risk evaluation for patients with atrial fibrillation: Insights from left atrial appendage, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2022.968630, 9 Gonzalo A, García‐Villalba M, Rossini L, Durán E, Vigneault D, Martínez‐Legazpi P, Flores O, Bermejo J, McVeigh E, Kahn A and del Alamo J (2022) Non‐Newtonian blood rheology impacts left atrial stasis in patient‐specific simulations , International Journal for Numerical Methods in Biomedical Engineering, 10.1002/cnm.3597, 38:6, Online publication date: 1-Jun-2022. Saiz-Vivó M, Mill J, Harrison J, Jimenez-Pérez G, Legghe B, Iriart X, Cochet H, Piella G, Sermesant M and Camara O (2022) Unsupervised Machine Learning Exploration of Morphological and Haemodynamic Indices to Predict Thrombus Formation in the Left Atrial Appendage Statistical Atlases and Computational Models of the Heart. Regular and CMRxMotion Challenge Papers, 10.1007/978-3-031-23443-9_19, (200-210), . Althoff T and Mont L (2021) Prediction of stroke risk based on left atrial appendage morphology: from pareidolia to artificial intelligence, The International Journal of Cardiovascular Imaging, 10.1007/s10554-021-02307-y, 37:8, (2529-2531), Online publication date: 1-Aug-2021. Parra-Díaz P, Salido-Tahoces L, Pardo-Sanz A, Beltrán-Corbellini Á, Rodríguez-Jorge F, Chico-García J, García-Madrona S, Matute-Lozano C, Vera-Lechuga R, Cruz-Culebras A, Masjuan J and DeFelipe-Mimbrera A (2021) Malignant Left Atrial Appendage Morphology: Current Classification vs H-L System, Journal of Stroke and Cerebrovascular Diseases, 10.1016/j.jstrokecerebrovasdis.2020.105570, 30:3, (105570), Online publication date: 1-Mar-2021. February 2020Vol 13, Issue 2 Advertisement Article InformationMetrics © 2020 American Heart Association, Inc.https://doi.org/10.1161/CIRCEP.119.008074PMID: 31986073 Originally publishedJanuary 27, 2020 Keywordsatrial appendagestrokeatrial fibrillationtomographyangiographyPDF download Advertisement SubjectsCerebrovascular Disease/Stroke

Introduction: The insular cortex controls several aspects of vital function including autonomic regulation, and strokes affecting the insula have been associated with dysautonomia, cardiac dysfunction, and arrhythmias. Previous studies have shown an association between insular strokes, elevated troponin levels, and atrial fibrillation (AF). In this study, we aim to determine the association between cardiac biomarkers and insular involvement of the infarct and hypothesize that insular involvement implicates a cardioembolic source. Methods: We abstracted data from a prospective comprehensive stroke center registry of consecutive patients with a discharge diagnosis of acute ischemic stroke who underwent brain imaging (CT or MRI) and work up to determine stroke mechanism. Data included demographics, clinical baseline variables, laboratory tests (including admission troponin level), and transthoracic echocardiographic variables (regional wall motion abnormalities, ejection fraction, and left atrial volume index), and stroke subtype. Multivariable logistic regression models were built to determine associations between AF, and cardiac biomarkers and insular infarcts. Results: We identified 1224 patients who met the inclusion criteria; 397 (32.4%) had insular involvement of the infarct. In multivariable models, insular infarcts were associated with AF (adjusted OR 1.73, 95% CI 1.23-2.43, p = 0.001) and left atrial volume index (adjusted OR per standard deviation increase 1.30, 95% CI 1.13-1.49, p = 0.001). There was a trend for association between insular involvement and positive troponin level (adjusted OR 1.45 95% CI 0.91-2.33, p = 0.122) but not with regional wall motion abnormalities (adjusted OR 1.13, 95% CI 0.69-1.84, p = 0.627). Insular involvement was associated with cardioembolic stroke subtype (45.8% vs. 26.7%, p<0.001) but not other stroke subtypes. Conclusion: The insular cortex is commonly involved in patients with atrial fibrillation and/or atrial dilation and maybe a neuroimaging biomarker of cardioembolic stroke. Larger studies are needed to confirm this association and test anticoagulation therapy in patients with insular infarcts.

Background and Purpose: Previously we proposed a simple classification system of the left atrial appendage (LAA) morphology, with low risk (LAA-L) defined as one lobe with an acute angle bend arising from the proximal or middle portion and high risk (LAA-H) defined as all other morphologies. We aim to determine the association between LAA morphology (using both classification systems), LAA flow velocity, and stroke rates. Methods: We analyzed consecutive patients with atrial fibrillation (AF) selected for ablation who underwent cardiac CT angiography and transesophageal echocardiogram. The primary correlates were LAA-H and non-chicken wing (NCW) LAA morphology. The primary outcome was the composite endpoint of history of ischemic stroke/TIA or non-lacunar infarct on neuroimaging. Adjusting for CHADS2Vasc score, multivariable models were used to determine associations between LAA morphology and composite outcomes. Results: We identified 379 patients; the primary endpoint occurred in 32/379 patients (8.4%). LAA-H (adjusted OR 3.63, 95% CI 1.44-9.14) and NCW LAA morphology (adjusted OR 2.52, 95% CI 1.15-5.53) were associated with the primary endpoint. LAA flow velocity ≤20 cm/s was more common in LAA-H vs. LAA-L (9.6% vs. 2.8%, p = 0.019), but not in NCW vs. CW LAA morphology (9.7% vs. 3.7%, p = 0.054). Conclusion: The LAA H/L morphological classification system may be superior to the current system in risk stratifying patients with AF and correlates better with impaired LAA flow dynamics.

Family members of Veterans with posttraumatic stress disorder (PTSD) face high levels of burden that are poorly addressed by existing mental health services. Widely distributed mobile interventions could play a role in addressing these unmet needs. The purpose of this study was to characterize caregiver burden in those seeking a mobile app for self-management of stress symptoms and to develop a model to guide mobile interventions for family members. Those living with a Veteran with PTSD (n = 212) and interested in using a mobile intervention agreed to participate. The majority reported moderate-to-severe levels of depression (60%) and/or caregiver burden (59%). Relationship quality, communication, and self-efficacy for caregiving were the strongest predictors of negative outcomes (p's < .001), and qualitative results identified several additional unmet needs (e.g. relationship concerns, safety concerns). This study identifies potential mechanisms by which a mobile app could improve family functioning in the context of PTSD.

Introduction: Previous studies have shown an elevated risk of MI (MI) in patients with symptomatic intracranial atherosclerotic disease (sICAD), but the mediators of increased risk of MI or death in these patients remain uncertain. We aim to determine risk factors associated with MI or death in patients with symptomatic ICAD. Methods: Patients enrolled in SAMMPRIS had sICAD and were randomized to aggressive medical management (AMM) vs. stenting and AMM. The primary outcome of this post-hoc analysis is MI or vascular death within 2 years of follow-up. We excluded patients who were lost to follow up, had a stroke during follow up, had non-vascular death or death within 30 days of stenting. Patients meeting the inclusion criteria were divided into two groups: those with vs. those without the primary outcome. We used binary logistic regression to determine predictors of incident MI or death within 2 years. Results: Of the 451 patients enrolled in SAMMPRIS, 350 patients met the inclusion criteria (reasons for exclusion: 4 deaths occurring within 30 days of stenting, 63 with ischemic stroke, 6 with symptomatic hemorrhage, 7 patients with non-cardiovascular death within 2 years, and 21 lost to follow up). At 2 years, 17 patients (4.9%) had MI/death; 10 patients had MI and 7 had cardiovascular deaths. In a multivariable model, factors associated with MI/death were: history of coronary artery disease (adjusted OR 3.19, 95% CI 1.14 - 8.93, p = 0.027) and systolic blood pressure (adjusted OR per 10 mm increase 1.20, 95% CI 0.98 - 1.44, p = 0.080). This risk was abut 24% with both predictors present and 2.8% with them absent (Figure). Conclusion: Higher systolic blood pressure and pre-existing cardiovascular disease were independently associated with incident MI or vascular death in patients with sICAD, despite medical management. Further studies are needed to confirm this association and test interventions to reduce this risk.

Monday, April 27April 14, 2020Free AccessMeasurement of Left Atrial Appendage Flow Velocity to Enhance Risk Assessment for Stroke in Atrial Fibrillation Patients (446)Eric Zhou, Andrew Chang, Nikhil Panda, Antony Chu, Karen Furie, Michael Atalay, Christopher Song, and Shadi YaghiAuthors Info & AffiliationsApril 14, 2020 issue94 (15_supplement)https://doi.org/10.1212/WNL.94.15_supplement.446 Letters to the Editor

Background: The left atrial appendage (LAA) is the main source of thrombus in atrial fibrillation (AF); biomarkers of LAA dysfunction are associated with ischemic stroke (IS) risk in patients with AF. We hypothesized that high risk LAA features [High risk morphology (LAA-H), LAA volume (LAAV), and LAA orifice surface area (LAAOSA)] would be more prevalent among patients with cardioembolic (CE) stroke and embolic stroke of undetermined source (ESUS) than among those with non-cardioembolic stroke (NCS). Methods: Consecutive patients with IS from a prospective comprehensive stroke center registry who previously underwent a clinically-indicated qualifying chest CT were included. Patients underwent inpatient diagnostic evaluation for ischemic stroke, and stroke subtype was determined based on ESUS criteria. LAA morphology [Low risk morphology was defined as two lobes with an acute angle between them or chicken wing morphology and LAA-H defined as all others], LAAOSA (measured in a plane parallel to the left atrium), and LAAV (measured using a volumetric analysis software) were determined using contrast enhanced thin-slice chest CT (≤2.5 mm thickness) by investigators blinded to stroke subtype. Results: Of 1234 patients with ischemic stroke, 329 (26.7%) patients had a qualifying chest CT performed (126 CE, 116 ESUS, and 87 NCS). The baseline characteristics of patients with and without chest CT were similar. When compared to NCS, LAA-H was more prevalent in ESUS (86.4% vs. 70.1%, p=0.018) and CE stroke (82.5% vs. 70.1%, p=0.042). The LAAOSA and volume did not significantly differ between the 3 groups (Table). Conclusion: LAA characteristics associated with cardioembolic stroke are also more prevalent in patients with ESUS. Larger studies are needed to confirm that LAA features are a risk factor for stroke among patients without AF, and whether anticoagulation is effective in patients with high-risk LAA features.

Background: There is evidence that suggests that a LAMS >/= 4 is a good predictor of LVO and this threshold is oftentimes used to triage stroke patients in the field to the nearest comprehensive stroke center. In this study, we aim to determine whether atrial fibrillation (AF) can improve the ability of LAMS in predicting LVO. Methods: We included consecutive patients with a diagnosis of ischemic stroke admitted within 24 hours from last known normal time who underwent emergent vascular imaging using a computerized tomography angiography (CTA) of the head and neck. LVO was defined as intracranial internal carotid artery, proximal middle cerebral artery (M1 or proximal M2 segment), or basilar occlusion. We defined atrial fibrillation (AF) as history of AF or telemetry in the emergency department showing AF. The LAMS score was determined in the ED upon arrival. Univariate and multivariable models were performed to identify predictors of LVO and to determine whether AF improves the ability of LAMS to predict LVO. Results: Among 1234 patients admitted to our institution within the study period, 862 underwent emergent vascular imaging (69.8%) out of which 374 (43.4%) had evidence of LVO and 207 (24%) underwent mechanical thrombectomy. After adjusting for confounders, independent predictors of LVO were LAMS (adjusted OR 1.42 per one point increase 95% CI 1.29-1.57) and AF (OR 1.95 95% CI 1.26-3.02, p<0.001) (Table 2). We developed the LAMS-AF that includes the LAMS score and adds 2 points if AF is present. In this analysis, LAMS-AF (AUC 0.78) was superior to LAMS (AUC 0.76) in predicting LVO (Figure). Results remained unchanged when thrombectomy was used as outcome. Using LAMS-AF lead to re-classification of 8/68 patients (11.8%) in the LAMS=3 group into the high-risk LVO group (Table 3) Conclusion: In patients with LAMS=3, using the LAMS-AF score may improve the ability of LAMS in predicting LVO. More studies are needed to confirm our findings particularly using field LAMS.

Introduction: Although studies have examined emergent CTAs of the head and neck in patients seen by neurologists who are suspected of having a large vessel occlusion, the utility and accuracy of CTA for patients called as a ‘code stroke’ by any healthcare provider has not been evaluated. Methods: At our institution, imaging for all Code Stroke patients includes non-contrast CT of the brain as well as CTA of the neck and brain, regardless of severity. This imaging is often performed prior to detailed neurology evaluation. We queried our radiology department report database for all studies labelled ‘CTA ELVO’, an imaging order code which is specific for Code Stroke. We then cross-referenced this list with our prospectively acquired ischemic stroke registry, which consists of all patients discharged with a diagnosis of acute ischemic stroke. Results: Between January and August 2017, 1265 CTA ELVOs were performed. Average age was 66.3 years, and 52.4% were female. Of all CTA ELVOs, 144 were performed on inpatients (11.3%) and neuroradiologists read 149 studies (11.8%). Critical findings on vessel imaging were present in 165 studies (13%); of these 118 patients were ultimately diagnosed with acute ischemic stroke. Studies with critical findings involved older patients (73.7 years, p<0.001) and were less likely to be performed on inpatients (29 studies, p=0.012) but were no different in number of females (55%, p=0.51) or whether read by a neuroradiologist (23 studies, p=0.36). Critical findings included acute intracranial large vessel occlusion involving the middle cerebral artery, intracranial internal carotid artery (ICA), or basilar artery (87 studies); critical cervical ICA stenosis, acute cervical ICA occlusion, or acute dissection (42 studies); M2 occlusion (32 studies); critical intracranial stenosis (7 studies) and vascular malformation such as aneurysm or arteriovenous malformation (6 studies). Conclusion: The yield of non-invasive vessel imaging in patients called as a code stroke in detecting critical findings is high, revealing abnormalities in approximately one in eight patients. Patients presenting with acute neurologic symptoms should receive vessel imaging as part of the initial workup for suspected stroke.