tbuckley/cabot-search huggingface dataset:
Abstract 16818: Frozen in Time: Endothelial Progenitor Cell-Derived Extracellular Vesicles Maintain Therapeutic Efficacy for Clinically Translatable Treatment of Acute Myocardial Infarction After Long Term Storage
Authors: Jennifer J Chung, Samir Zaman, Maria F Arisi, Elizabeth Li, Minna H Chen, Carol W Chen, Ann C Gaffey, Jason A Burdick, Pavan Atluri
Journal: Circulation (2018)

Introduction: Extracellular vesicles (EV) derived from progenitor cells are a novel therapy for ischemic cardiomyopathy, with promise for “off-the-shelf” delivery. Clinical translation and timely delivery post-myocardial infarction (MI) requires assurance of EV stability after storage. Bioactivity studies of EVs after freezing are currently lacking and are necessary to establish quality standards for widespread clinical use of EVs. Hypothesis: We hypothesize that endothelial progenitor cell-derived EVs (EPC-EVs) can be frozen at -80 °C for at least 2 months without decrement of therapeutic effect when delivered intramyocardially to ischemic tissue. Methods: EVs were isolated from male Wistar rat bone marrow EPCs. Fresh preparations of EVs isolated from 700,000 EPCs were compared to frozen EVs stored in dPBS for 2-4 months at -80 °C. Particle size of EVs was analyzed via nanoparticle tracking analysis. In vitro angiogenesis was measured with Matrigel assay. A rat model of MI via left anterior descending artery ligation was used to assess EPC-EV function. Hemodynamics, scar thickness and vasculogenesis were assessed 4 weeks post-intramyocardial injection of EPC-EV within a shear-thinning gel (STG). Results: After 4 months’ storage at -80 °C, frozen EVs had stable mean particle diameter. In vivo analysis demonstrated equivalent hemodynamic outcomes between fresh and 2-month frozen EVs (p=1.0), both of which had statistically significantly improved measures of contractility over PBS as measured by Ees (p=0.0001; p=0.0008) and dp/dt (p=0.01; p=0.03, respectively). Scar thickness was increased in fresh, but not frozen EVs vs PBS (0.68, 0.64 v 0.50; p=0.031, p=0.22). On IHC, fresh and frozen EVs had significantly increased vascular density vs PBS (Δ665.5, Δ907.5; p=0.05). Conclusions: EPC-EVs retain adequate functionality after 2 months of freezing to produce hemodynamic benefits equivalent to freshly prepared EPC-EVs when delivered in STG to ischemic myocardium.
Abstract 16833: Long-Term Outcomes and Complications of Anticoagulant Therapy for Bioprosthetic Valve Thrombosis in a Large Matched-Cohort Study
Authors: Ioana Petrescu, Filip Ionescu, Vuyisile T Nkomo, Heidi M Connolly, Patricia A Pellikka, Cristina Pislaru, Alexander C Egbe, Sorin V Pislaru
Journal: Circulation (2018)

Introduction: Bioprosthetic valve thrombosis (BPVT) is a well-recognized cause of prosthetic dysfunction. Anticoagulation restores prosthetic valve gradients, but long term outcomes and complications from therapy are unknown. Objectives: To define the complications and long-term outcomes of anticoagulant therapy for BPVT. Methods: Retrospective matched cohort study of patients treated with warfarin for presumed BPVT at a single center from 1999 to 2016. Controls with normal bioprostheses by echocardiography were matched 2:1 for age at implantation, gender, prosthetic valve position, and type of prosthesis (porcine / pericardial). Results: A total of 83 presumed BPVT patients (40 aortic, 21 mitral, 18 tricuspid, and 4 pulmonary) and 166 controls were included. Age at BPVT diagnosis was 60±19 yrs (41±41 months post implantation); 45 (54%) were male. Transvalvular gradients returned to baseline in 63 (76%) of the patients, after 5±4 months of warfarin; 60 (72%) patients were maintained on warfarin indefinitely. Recurrent BPVT was seen in 13 (16%) patients, 33±31 months after initial therapy. When compared to controls, warfarin-treated BPVT patients had similar incidence of stroke [4(5%) vs 5 (3%), p=0.49], peripheral embolic events [4(5%) vs 10 (6%), p=0.78)], and death [12 (14%) vs 28 (17%), p= 0.72] (Figure, left panel), but more bleeding requiring transfusion [18 (22%) vs 3 (2%), p&lt;0.0001]. Presumed BPVT patients more often required surgical or percutaneous valve re-replacement (Figure, center panel); this difference persisted even when comparing only patients with confirmed BPVT (those who responded to anticoagulant therapy) vs. their matched controls (Figure, right panel). Conclusion: Warfarin anticoagulation for presumed BPVT is successful in the majority of patients, without increase in stroke, peripheral embolism or death, but at the cost of excess bleeding. Recurrent BPVT occured in 16% of patients. Importantly, patients with BPVT required more often valve re-replacement. This finding suggests that anticoagulant therapy does not fully restore prosthetic valve durability, and that BPVT patients should be closely monitored.
Abstract 16999: Effect of Positional Echocardiogram on Right Sided Hemodynamics in Pectus Excavatum Patients vs. Healthy Adults
Authors: Venkata Siva Krishna Pulivarthi, Dawn Jaroszewski, Reza Arsanjani, Farouk Mookadam
Journal: Circulation (2018)

Introduction: Pectus excavatum (PE) is the most common anterior chest wall deformity with dorsal deviation into the thoracic cavity. Depending on the severity, PE can cause minor cosmetic problem to significant cardiac compression in severe cases. This compression most frequently affects right heart chambers causing symptoms such as dyspnea, palpitations, fatigue, exercise intolerance, and difficulty with keeping up with peers. Previously, we reported the change in these symptoms with positon associated with change in right heart hemodynamics. Further, we are comparing the changes in right heart hemodynamics with position in pectus patients to normal healthy adults. Methods: A prospective cohort of 40 pectus excavatum patients (mean Haller index: 5.4±2) undergoing evaluation at Mayo clinic underwent 2-D transthoracic echo (TTE) with Doppler assessment of Right Ventricular Outflow Tract (RVOT) Velocity Time Integral (VTI). A cohort of 8 healthy adults without chest wall abnormality who had clinically indicated echocardiogram was used as control (Table). Additional assessment of the RVOT VTI was performed in sitting position in either group. A two-sample t-test was performed to assess significance between cohorts. Results: There is a significant difference in RVOT VTI between case and control cohorts in both supine and sitting positions (p=0.03 &amp; p=0.001 respectively). Also, there is a significant decrease in RVOT VTI from supine to sitting position in PE patients compared to healthy adults (Table). Conclusion: This is the 1 st prospective cohort study in PE patients vs healthy adults showing the feasibility and utility of dynamic echocardiography in assessing the right ventricular hemodynamics. This study demonstrates a significant decrease in right sided hemodynamic changes with change in position in patients with PE which might explain their symptoms.
Abstract 16634: Preoperative Biomarkers of Inflammation and Oxidative Stress Predict Early Outcomes and Only Modestly Decline After Left Ventricular Assist Device Implantation: A Prospective Study
Authors: Melana Yuzefpolskaya, Mojdeh Nasiri, Alberto Pinsino, Hatice D Onat, Amelia M Zuver, Joseph K Nwokocha, Eugene A Royzman, Melissa Mabasa, Autumn M Clemons, Francesco Castagna, Arthur R Garan, Danielle L Brunjes, Koji Takeda, Hiroo Takayama, Yoshifumi Naka, Anne-Catrin Uhlemann, Paolo C Colombo, Ryan T Demmer
Journal: Circulation (2018)

Background: Inflammation and oxidative stress play a pivotal role in pathogenesis of heart failure (HF). Left ventricular assist device (LVAD) is a durable option for treatment of advanced HF, however i) trends of inflammatory and oxidative biomarkers over time are unknown and ii) complications such as right ventricular failure (RVF), stroke and renal failure remain high. The aims of this study were to: i) study longitudinal patterns of inflammation and oxidative stress in LVAD pts and ii) create a biomarker score to identify pts at risk for early adverse events. Methods: We prospectively studied 67 pts (166 samples): pre-LVAD n=56; LVAD (1mo; n=45); LVAD (3-6mo; n=39); LVAD (9-12mo; n=18) and LVAD (18mo; n=8). Inflammatory/oxidative biomarkers: adiponectin, C-reactive protein (CRP), endothelin-1(ET1), interleukin-6 (IL6), tumor necrosis factor- α (TNF α), isoprostane(IsoP), soluble (sCD14), trimethylamine N-oxide (TMAO) were measured in blood. Adverse events including death, stroke, RV failure, and renal replacement therapy (RRT) during implant admission were collected. A pre-LVAD biomarker score was calculated accounting for the number of biomarkers greater than median. Composite event was combination of death, stroke, RV failure and RRT. The RV failure and composite event rates were tested against the biomarker score (&lt;median vs ≥median). Results: Pts were 58±14 yo, 87% male. TMAO and IsoP decreased at 1 mo, then rebounded modestly. ET1, CRP, and IL6 increased at 1 mo and subsequently declined (Table). Adverse event rates were higher in the biomarker score ≥median vs &lt;median: RV failure occurred in 14 (47%) vs 4 (19%) (p=0.042); composite event rate occurred in 14 (47%) vs 5 (24%) (p=0.097). Conclusion: LVADs reduce the degree of inflammation and oxidative stress in advanced HF within the first 3mo, however reductions are modest and biomarkers do not normalize. Pre LVAD elevation of biomarkers can identify pts at risk for early adverse events.
Abstract 13739: Emergency Medical Services Calls During COVID-19: Bottleneck Explained&amp;lt;A Narrative Review&amp;gt;
Authors: Alaa Al Amiry, Brian Maguire
Journal: Circulation (2021)

Background: During COVID-19 peak in 2020, EMS calls have surged unprecedently internationally, causing global disruption in EMS dispatch centers’ services and significant delays in emergency response worldwide. This negatively impacted the chain of survival for cardiac and stroke, and other emergencies. No studies yet have been done to examine this phenomenon globally. Objectives: This paper examines the interrelated effects of the unprecedented global increase of EMS calls, the effect of the COVID-19 crisis on responding to non-COVID-19 emergencies; mainly cardiac and stroke emergencies- among others, and the concurrent effects of having overwhelmed dispatch centers. We examined the bottleneck phenomenon that resulted in the disruption of EMS calls in different countries, and found three main factors: 1.EMS-related factors 2.Social-related factors 3.Patient-related factors. For better understanding, we also explained each factor based on the available literature. Eligibility Criteria : We examined the numbers of EMS calls internationally between March and June 2020, derived from published literature and news media. Only articles in English were selected, with certain keywords related to EMS calls, ambulance delay, stroke and cardiac arrest. Results: After applying the selection criteria, a total of 29 citations were chosen, and a pattern of knowledge resulted in the emergence of five themes: •EMS calls during COVID-19 •Reduced EMS operator response time •Ambulance response delays •Collateral mortality and morbidity among non-COVID-19 cases •Total ambulance call time Conclusion: Over the course of COVID-19 progress, there was a global phenomenon of exponential increases in EMS calls, which is expected to impose a great pressure on EMS dispatch centers. Several factors contributing to the bottleneck of EMS calls are identified and explained. By understanding these factors and their collateral impact on EMS calls, we can implement better crises and disaster response plans. This is an informative paper to EMS decision makers worldwide. Key words: EMS calls, COVID-19, Ambulance response time, Pandemic response, EMS access, Ambulance delay
Abstract 16749: ET <sub>B</sub> Receptor Agonist, IRL-1620, Decreased Cerebral Ischemic Damage by Decreasing Fission and Increasing Fusion of Mitochondria in Rat
Authors: Seema Briyal, Sandra Luu, Anil Gulati
Journal: Circulation (2018)

Introduction: We have shown that endothelin B (ET B ) receptor agonist, IRL-1620, provides neuroprotection by inhibiting apoptosis in rats. Mitochondrial dysfunction has been implicated in the cell death following ischemia. Hypothesis: IRL-1620 prevents neuronal death by altering mitochondrial activity. Methods: We determined the effect of IRL-1620 on mitochondrial dysfunction following cerebral ischemia. Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO). Following surgery, rats received intravenous injections of vehicle or IRL-1620 (5 μg/kg, i.v.) at 4, 6, and 8 hr post-occlusion on day 0; similar treatment of vehicle or IRL-1620 was repeated on day 3 and 6 post-MCAO. Animals were sacrificed at 24 hr and day 7 following occlusion and brains processed to evaluate expression of mitochondrial dysfunction markers (DRP-1, MFN-2 and ATP5A) using immunofluorescence and western blot. Results: Animals treated with IRL-1620 showed significant improvement in all neurological and motor function tests compared with vehicle-treated group. At 24 h and day 7 following MCAO, a significant increase in DRP-1 (a key mediator of mitochondrial fission) and decrease in MFN-2 (key mediator of mitochondrial fusion) was observed in the vehicle-treated group compared to sham group. IRL-1620 treatment significantly [F(5,18)=10.5, p&lt;0.001] decreased (-53%) expression of DRP-1 and significantly [F(5,18)=25.78, p&lt;0.0001] increased (165%) expression of MFN-2 in MCAO rats compared to vehicle treated rats. There were no changes in ATP5A expression levels in the brains of sham, vehicle, and IRL-1620 treated rats 24 h post occlusion. A significant [F(5,18)=11.38, p=0.011] increase (70%) in ATP5A in the vehicle group was observed on day 7 compared to sham. However, IRL-1620 significantly [F(5,18)=11.38, p=0.0009] decreased (-53%) the expression of ATP5A in MCAO rats compared to vehicle. Immunofluorescence studies corroborated Western blot results showing an increase of DRP1 and a decrease of MFN-2 positive cells in the vehicle group after 24 hr and day 7 compared to sham group. These changes were reversed in IRL-1620 treated rats. Conclusions: Stimulation of ET B receptors with IRL-1620 is neuroprotective in a rat model of cerebral ischemia by decreasing (DRP-1) fission and increasing (MFN-2) fusion of mitochondria.
Abstract 16832: Cardiovascular Health Study of Emerging Adults Entering College: Implications for Prevention Research
Authors: Angela F Pfammatter, Shirlene Wang, Susan H Hood, Alexa Mitsos, Bonnie Spring
Journal: Circulation (2018)

Introduction: Cardiovascular disease is a significant societal burden and the college years are a time of risk for loss of cardiovascular health (CVH). Whereas 50% of individuals under age 19 have ideal levels in five of American Heart Association (AHA) Life’s Simple Seven (LS7), that number declines to 16% by young adulthood. NUYou, a randomized clinical trial in AHA’s Strategically Focused Prevention Research Network, tests the feasibility, acceptability, and effectiveness of a mobile health technology supported intervention. To our knowledge, this is the first trial assessing and intervening on multiple behaviors in the college student population for the purpose of preserving CVH. Methods: Freshmen were recruited via multiple strategies and cluster randomized by dormitory to receive intervention targeting four CVH related behaviors or four non CVH related behaviors for two years. Baseline CVH was measured using LS7 criteria. During in-person baseline visits, blood pressure, breath carbon monoxide, height, weight, glucose and cholesterol were measured and participants reported diet and physical activity. Results: Participants (N=303) were 60% female, and 50% White (12% Hispanic/Latinx), 28% Asian, 10% African American. 92% had ideal BP (Systolic M=100.75, SD 0.48; Diastolic M=63.44, SD=0.42), glucose (M=86.15, SD=0.87), and cholesterol (M=155.52, SD=1.67). In contrast, Figure 1 shows 29% of students met ideal physical activity levels and 2% met ideal diet quality (8% reported eating 5-7 servings of fruits and vegetables daily). Ideal levels of 5 LS7 factors were met by 71%. Conclusions: CVH among elite college freshmen was better than previous findings in this age group, largely due to a majority of students with ideal levels of BP, cholesterol, and glucose. Behavioral metrics were poorer, as a minority had ideal levels of diet and physical activity. The NUYou trial will track the trajectory of CVH and whether CVH is preserved by a mobile health intervention.
Abstract 16736: Etiology of Sudden Cardiac Arrest in Young Primary and Referral Populations: The Mayo Clinic Experience
Authors: Luis G Rodriguez-Cartagena, J. Martijn Bos, John R Giudicessi, Michael J Ackerman
Journal: Circulation (2018)

Introduction: The incidence and etiologies underlying sudden cardiac arrest (SCA) in the young are derived from population- and referral-based cohorts of young SCA survivors. The extent to which the use of these cohorts contributes to discrepancies in our understanding of SCA in the young is unknown. As such, we sought to determine and compare the spectrum of SCA etiologies observed in young SCA survivors evaluated at a single tertiary center on both a primary and referral basis. Methods: Retrospective review of 940 young SCA survivors evaluated between 1990 and 2017 was used to identify all individuals ≤ 50 years of age that experienced a SCA. SCA root cause was determined by review of the medical records and diagnoses classified as ischemic, primary electrical, structural, or unexplained. SCA survivors that initially presented to our institution were classified as primary, while those who presented for secondary evaluation received a referral classification. Results: Overall, 566 SCA survivors were identified (age at event 33 ± 14 years; 39% females). In comparison to primary SCA survivors, referral SCA survivors were younger at the time of SCA (39 ± 12 vs. 30 ± 14 years; p&lt;0.0001) and less likely to experience pre-SCA symptoms (45% vs. 27%; p&lt;0.0001). Among all SCA survivors, the most common etiologies were idiopathic ventricular fibrillation (27%), acute coronary syndrome (21%), long QT syndrome (10%), and hypertrophic (7%) and dilated (6%) cardiomyopathies. Ischemic etiologies were less common (45% vs. 25%; p&lt;0.0001) and primary electrical disorders more common (6% vs. 23%; p&lt;0.0001) in referral SCA survivors. Conversely, genetic heart diseases (hypertrophic cardiomyopathy, long QT syndrome, etc.) were over-represented in referral cases (8% vs. 29%; p&lt;0.0001), whereas no difference was observed in the number of primary and referral SCAs that remained unexplained. Conclusion: This study demonstrates, for the first time, that differences in SCA root cause exist between young SCA survivors evaluated at the same tertiary medical center on a primary vs. referral basis. Ongoing comparison of SCA etiologies between primary and referral SCA survivors may help resolve discrepancies regarding the contribution of specific disorders to SCA in the young.
Abstract 11959: Left Atrial Size and Function in Children and Young Adults With Obstructive vs. Nonobstructive Hypertrophic Cardiomyopathy
Authors: Addison Gearhart, Iqbal El-Assad, Kimberlee Gauvreau, Steven D Colan, Ming H Chen
Journal: Circulation (2021)

Introduction: Left atrial (LA) strain has been recently used to improve assessment of left atrial (LA) function. In adults with hypertrophic cardiomyopathy (HCM), increased LA size and decreased LA strain are associated with LVOT obstruction (LVOTO) and higher risk for adverse cardiovascular outcomes. Scant data exists on the association of LA strain and size in children with HCM, comparing those with and without obstruction. Methods: For this pilot study, all patients from an existing pediatric BCH stress echo HCM registry who had adequate echocardiographic images to assess both LA size and strain were consecutively enrolled and retrospectively reviewed. Post-processing LA size and strain (reservoir and conduit) were performed with use of Tomtec/Philips LV strain. Children with HCM were divided into 2 groups: those with resting LVOT gradients &lt;30 mm Hg (no obstruction) versus ≥30 mm Hg (obstruction). LA size, strain and diastolic indices were compared for those with and without obstruction. Results: A total of 48 children (63% male, median age 13 yrs, range 6-23yrs) with HCM and analyzable images from the registry formed the cohort. Patient demographics, LA size and strain, and diastolic indices are summarized in Table 1. HCM children with LVOTO had larger LA size (apical 4-chamber (A4C) cross sectional area: p&lt;0.001), lower LA conduit and reservoir strain (p&lt;0.05 for all), and increased diastolic dysfunction (p&lt;0.05 for all). Conclusions: Despite their younger age, children with obstructive HCM had larger LA size, lower LA reservoir and conduit strain, and increased diastolic dysfunction compared to children with nonobstructive HCM. Larger studies are needed with longer follow-up time to assess association of LA strain with cardiac events in children.
Abstract 16653: Coronary Artery Calcium, SPRINT Eligibility and Role of Risk Prediction for Intensive Blood Pressure Therapy: The Coronary Artery Calcium Consortium
Authors: S M Iftekhar Uddin, Mohammadhassan Mirbolouk, Sina Kianoush, Olusola A Orimoloye, Zeina Dardari, Garth Graham, Seamus P Whelton, Michael D Miedema, Khurram Nasir, John Rumberger, Leslee J Shaw, Daniel S Berman, Mathew J Budoff, John W McEvoy, Kunihiro Matsushita, Michael J Blaha
Journal: Circulation (2018)

Introduction: Coronary artery calcium (CAC) is a strong predictor of future cardiovascular events. We assessed whether CAC scoring could be used to identify hypertensive adults aged &gt;50 years who have cardiovascular disease (CVD) mortality rates similar to those observed in the Systolic Blood Pressure Intervention Trial (SPRINT) and who therefore might benefit from intensive blood pressure therapy. In addition, we examined the ability of CAC to stratify CVD risk among hypertensive adults, including those who are eligible for SPRINT. Methods: We studied 16,167 hypertensive adults from the CAC Consortium, among whom 5,163 were SPRINT-eligible (age &gt;50 years, Framingham Risk Score &gt;15%, and no diabetes mellitus). In order to determine what CAC scores were associated with CVD mortality rate observed in the standard-treatment group of SPRINT (0.43%/year), this rate was first age-standardized to the population structure of the CAC Consortium (age-standardized annual CVD mortality rate = 0.35%/year). A CAC-CVD mortality plot was then generated. A y-axis line was placed at the age-standardized CVD mortality rate, and its intersection with the CAC-CVD mortality plot was interpreted as the CAC-score equivalent of SPRINT-level risk. We also compared multivariable-adjusted hazard ratios of coronary heart disease (CHD) and CVD deaths by CAC category (0, 1-100, 100-400, &gt;400). Results: Mean age of the study population was 58.1±10.6 years. Over a mean follow-up of 11.6±3.6 years, there were 409 CVD and 207 CHD deaths. A CAC score of 220 (confidence range 165-270) was associated with the age-standardized CVD mortality rate observed in SPRINT. Additionally, increasing CAC scores were associated with increased CHD and CVD mortality in the overall study population [CHD - CAC 100-400: Hazard ratio (95% confidence interval) 1.9 (1.0-3.4), CAC&gt;400: 4.2 (2.3-7.4); CVD - CAC 100-400: 1.9 (1.3, 2.8), CAC&gt;400: 3.5 (2.4, 5.1)]. A similar pattern was observed in the SPRINT-eligible population. Conclusions: CAC risk stratifies adults with hypertension, including SPRINT-eligible adults. A CAC score of around 220 can identify hypertensive adults aged &gt;50 years with CVD risk similar to SPRINT and may therefore help identify candidates for more intensive blood pressure therapy.