tbuckley/cabot-search huggingface dataset:
Abstract 13256: Efficient and Precise Phenotyping of Murine Fetal Hearts by Means of Synchrotron-Based Phase-Contrast Micro-Computed Tomography
Authors: Niccolo Peruzzi, Kinga I. Gawlik, Timothy Mead, Till Dreier, Elna Lampei, Jenny Romell, Suneel S Apte, Martin Bech, Anne Bonnin, Karin Tran-Lundmark
Journal: Circulation (2023)

Mouse models are routinely utilized to investigate the role of genes in congenital heart disease. Cardiovascular phenotyping is, however, quite challenging because of the small size of fetal mouse hearts. The most used method is histological assessment, which typically provides only two-dimensional information and thus might overlook important structural defects. Three-dimensional (3D) methods with sufficient resolution are either time-consuming, require specific sample preparation and/or selective staining, or cause destruction of the sample. Here, synchrotron radiation-based phase-contrast micro-computed tomography (SRμCT) was evaluated for fast and precise phenotyping of unstained, intact murine fetal hearts in a non-destructive way. Embryonic day (E) 18.5 hearts from control mice and mice that lack the secreted protease ADAMTS6 were formalin-fixed, paraffin-embedded and then scanned with SRμCT at the TOMCAT beamline (Swiss Light Source) with a 1.63 μm effective pixel size. Following SRμCT, the hearts were sectioned and processed for standard hematoxylin and eosin staining (H&amp;E), and for specific immunofluorescence staining. SRμCT enabled evaluation of the hearts with a high level of detail. A full E18.5 mouse heart was scanned in less than 3 minutes, followed by virtual sectioning along arbitrary slicing planes and 3D rendering for morphological assessment. The resolution proved sufficient to trace minute features like the coronary arteries. In the Adamts6 knockouts, malformations such as a ventricular septal defect and double outlet right ventricle could be readily diagnosed. We also explored the potential of merging stained sections with SRμCT. In summary, SRμCT has the potential to become a powerful tool for fast phenotyping of mutant mouse models. The combination of 3D imaging with subsequent sectioning and methods like histology, immunohistochemistry and in situ hybridization will uncover pathophysiological mechanisms in 3D space.
Abstract 15771: Cardiosphere-Derived Cell Extracellular Vesicles (CDC-EVs) Alter C-C Chemokine Receptor Type 2 (CCR2) Mediated Monocyte Pro-Inflammatory Signaling Following Cardiac Injury
Authors: Touba Tarvirdizadeh, Rohan Pandey, Kyle I Mentkowski, Paul Schiffmacher, Lisa Eagler, Jessica Reynolds, Jennifer K Lang
Journal: Circulation (2023)

Background: Following cardiac damage, CCL2 (a cytokine released by the injured cardiac tissue) recruits CCR2+ monocytes to the site of injury. Heightened CCL2 levels, however, can over activate the CCR2+ mediated pro-inflammatory response leading to poor cardiac healing. Cardiosphere-derived cell extracellular vesicles (CDC-EVs) have been shown to suppress the inflammatory response by decreasing CCR2 monocyte expression. We hypothesized that treatment with CDC-EVs would suppress CCR2 expression of peripheral monocyte in patients with acute MI. Methods: A prospective single arm observational study was performed. Inpatients at Buffalo General Medical Center were recruited following these criteria: 1) &gt;18 years of age AND 2) a type I MI. Subjects were excluded for the following: 1) fever in last 2 days/infection, 2) is or may be pregnant, or 3) currently undergoing cancer treatment. Monocytes were isolated from peripheral blood samples using Ficoll/centrifugation followed by magnetic activated cell sorting. Isolated monocytes were incubated with either PBS, normal human dermal fibroblast EVs (NHDF-EVs) or CDC-EVs. Monocytes then were analyzed for CCR2 expression by flow cytometry. Multi-variate analysis was performed. Results: CDC-EVs significantly reduced classical monocyte expression of CCR2 by 23% as quantified by flow cytometry compared with PBS (p&lt;0.05, one way ANOVA, n=23) and by 13% compared with NHDF-EVs (p&lt;0.05, one way ANOVA, n=23) in patients with recent MI. This reduction was seen regardless of patients’ pre-existing co-morbidities, medications, LVEF, or history of PCI. Smoking was associated with decreased response to CDC-EV mediated CCR2 suppression (Linear regression model R -0.93, p&lt;0.05, n=23). Conclusions: CDC-EVs effectively downregulate CCR2 expression in patients with recent MI, representing a potential adjunct to current clinical therapies in patients with a heightened pro-inflammatory response post-MI.
Abstract 17641: Frequency of Reported Euglycemic Ketoacidosis With Sodium-Glucose Cotransporter-2 Inhibitors is Not Increased in Patients With Heart Failure: Analysis of US Food and Drug Administration Adverse Event Reporting System (FAERS)
Authors: Samantha L Yeung, Mengxi Wang, Mimi Lou, Tien M Ng
Journal: Circulation (2023)

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are first-line therapy for heart failure (HF) but have an associated risk for euglycemic ketoacidosis. Patients with HF exhibit many additional risk factors for euglycemic ketoacidosis. However, no data describes the incidence or risk of euglycemic ketoacidosis in HF. Hypothesis: Reported incidence of euglycemic ketoacidosis with empagliflozin and dapagliflozin is not higher in patients with HF compared to the general population. Methods: Cases of euglycemic ketoacidosis with empagliflozin and dapagliflozin (single or combination products) were identified in the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2022 to March 2023. HF was identified as those taking at least two of the listed medication categories (angiotensin converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitor, mineralocorticoid receptor antagonist, HF-approved beta blocker) with a loop diuretic or search terms related to cardiac failure from MedDRA. Cases with missing event date, age, gender, and reporter country were removed. Reporting rates of euglycemic ketoacidosis stratified by HF status were examined descriptively. Results: Out of 16,880 adverse event reports involving empagliflozin and dapagliflozin, a total of 432 (2.6%) cases of SGLT2 inhibitor-associated euglycemic ketoacidosis were identified (mean age 65±13 years, 55.6% male, and mean weight of 87±27 kg). Patients who developed euglycemic ketoacidosis were younger and of lower mean weight. The incidence of euglycemic ketoacidosis among patients without HF was 2.8% compared to 0.8% in patients with HF [OR 0.27, 95% CI (0.17, 0.44)]. Mortality or need for hospitalization was not increased in patients experiencing euglycemic ketoacidosis for both the HF cohort (mortality: 5.9% vs. 6.7%; hospitalization: 23.5% vs. 31.1%) and general population (mortality: 0.2% vs. 3.6%; hospitalization: 30.1% vs. 27.3%). Conclusions: Euglycemic ketoacidosis with empagliflozin and dapagliflozin was uncommon, does not appear to be more frequent in patients with HF compared to the general population, and does not appear to be associated with worse outcomes.
Abstract 17255: Local Gunfire Exposure is Associated With Acutely Increased Blood Pressure on the South Side of Chicago
Authors: Joanna O Obaoye, Yu Zhou, Rhys F Chua, Mustafa Agha Al Kola, Corey E Tabit
Journal: Circulation (2023)

Hypertension is a leading risk factor for cardiovascular disease, which is especially prevalent among minority urban patients. Our group and others have previously shown that socio-environmental factors such as crime and poverty raise cardiovascular risk. However, the acute effects of local urban gunfire on patients’ blood pressure are unknown. We hypothesized that local gunfire in our South Side Chicago community was temporally associated with an acute rise in blood pressure for nearby patients. We performed a retrospective cohort study including 7,564 patients aged 18-104 who completed two or more outpatient clinic visits within 1 year at our academic tertiary-care center on the South Side of Chicago. We included 41,554 pre-pandemic clinic visits and recorded the blood pressure for each visit. Local gunfire was measured using ShotSpotter®, a network of microphones installed throughout the South Side of Chicago, which locates gunshots using auditory triangulation. Datasets of gunfire incidents are publically available from ShotSpotter® including date/time and geolocation of incidents. We focused on incidents that occurred within 1 km of each patient’s address and between two clinic visit dates (33 days, on average). Our primary outcome was the change in systolic blood pressure between the two clinic appointments. We excluded patients whose antihypertensive regimen was changed at the first appointment. Next, we utilized a multivariate regression model to assess the relationship between incidents of gunfire and seasonally-adjusted changes in blood pressure. Between-visit gunshot exposure ranged from 1 to 1,793 per patient. We found that each incident of gunfire was associated with a statistically significant acute increase in systolic blood pressure (0.0033 mmHg increase per gunfire incident [0.0022, 0.0044], p&lt;0.0001). Results were similar regardless of whether total round count or total gunfire incidents were considered. In this study of urban patients, incidence of gunfire within 1 km of a patient’s address was associated with an acute rise in blood pressure over approximately 1 month. These findings implicate the adverse impact of local gunfire exposure and environmental stress on blood pressure in adults on the South Side of Chicago.
Abstract 15320: Trends in Pulmonary Embolism-Related Mortality in the United States Before and During the COVID-19 Pandemic
Authors: Milan Kaushik, Haibin Li, Frank Qian, Brett Carroll
Journal: Circulation (2023)

Introduction: Infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2) and the subsequent development of COVID-19 is associated with an increased risk of pulmonary embolisms (PE). We sought to determine the trends in PE-related mortality in the United States from 1999 to 2021. Methods: We analyzed all deaths occurring in the US using the US Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database from 1999 to 2021. The Multiple Cause-of-Death Public Use record death certificates were used to select PEs as the primary or contributing cause of death using relevant ICD-10 codes. PE-related age-adjusted mortality rates (AAMR) per 100,000 persons were calculated and standardized to the US population in 2000. We calculated annual percent changes (APC) and corresponding 95% confidence intervals (CI). We also conducted subgroup analyses to examine mortality trends by age, sex, and racial/ethnic groups. Results: From 1999 to 2013 and between 2013 and 2019, APC for PE-related mortality remained relatively stable, corresponding to -0.4% (95% CI: -0.6 to -0.2) and 1.3% (95% CI: 0.6 to 2.1), respectively. Between 2019 and 2021, PE-related mortality increased from 9.2 to 14.1 per 100,000 populations per year, corresponding to an APC of 21.7% (95% CI: 18.3 to 25.3). There was a similar pattern of increase among individuals &lt; or ≥65 years. Men had a significantly greater increase in APC, 24.6% (95% CI: 20.5 to 28.9), when compared to women, 18.9% (95% CI: 15.0 to 22.9). All racial/ethnic groups experienced an increase in PE-related mortality between 2019 and 2021 but the increase was more pronounced among minority groups including Non-Hispanic Blacks, Hispanics and Native American/Alaskan Natives. Conclusion: PE-related mortality significantly increased during the COVID pandemic, and the increase was disproportionately greater among men and racial/ethnic minorities.
Abstract 18142: A Silent Heart Break: An Uncommon Case of Silent Mitral Valve Perforation Secondary to Infective Endocarditis
Authors: chris M agyingi, Olva Bess, Ahmed Gubran, Mohammed Alsillak, Ronny Cohen, Antoine Tabot
Journal: Circulation (2023)

Introduction: Infective Endocarditis (IE) is an endocardial surface infection of the heart which may lead to valve damage and if severe, this may even lead to valve perforation which can cause significant regurgitation and cardiac function compromise. We present an uncommon case of IE complicated by mitral valve perforation. Case presentation: A 46-year old male with AIDS and polysubstance use was brought to the ED from a shelter after exhibiting erratic behavior with confusion. On exam, he was febrile and tachycardic. Lab data pertinent for lacticaemia and leukocytosis. Blood cultures grew Streptococcus Pneumoniae. MRI Brain was unremarkable. Echocardiography was unremarkable. Antibiotic was initiated leading to marked improvement in patient’s mental status. Despite clinical improvement, days into hospital course, a new holosystolic murmur was audible with left axillary radiation necessitating a repeat echocardiogram which revealed moderate-to-severe mitral eccentric jet regurgitation concerning for anterior leaflet perforation. He remained euvolemic without symptoms of heart failure and was subsequently transferred to a tertiary facility where a mitral valve surgery replacement was scheduled. Discussion: Most patients with infective endocarditis have no preceding valvular abnormality. This case is unusual as there was valvular perforation with no evidence of valvular involvement on prior imaging which could possibly be as a result of invasive streptococcus pneumonia IE potentially coexisting with bacterial meningitis which carries a high mortality rate. Invasive streptococcus pneumonia is an unusual cause of IE since wide availability of antibiotics and vaccines. This case reminds us of the need of thorough physical exam and sequential imaging in such immunocompromised patient groups. Conclusions: A high suspicion for mitral valve perforation should be maintained in patients with invasive streptococcus pneumoniae and new cardiac murmur.
Abstract 16051: Heart Transplantation With a Positive Crossmatch in Pediatric Recipients is Associated With Increased Mortality in the Current Era: An Analysis of the United Network for Organ Sharing Database
Authors: Matthew J O'Connor, Courtney Vu, Xuemei Zhang, Steve Ampah, Jonathan J Edwards, Kimberly Lin, Katsuhide Maeda, Joseph Rossano, Carol Wittlieb-Weber, Jonathan B Edelson
Journal: Circulation (2023)

Introduction: Congenital heart disease (CHD) patients undergoing heart transplantation (HT) often have anti-HLA antibodies (sensitization), increasing the likelihood of a positive crossmatch and in turn an increased risk of mortality post-HT. The burden of sensitization in pediatric HT recipients and outcomes in such patients in the current era are unknown. Methods: The United Network for Organ Sharing (UNOS) database was queried for patients &lt;18 y/o with CHD undergoing HT between 4/1/2015 and 12/31/2019. Panel reactive antibody (PRA) at HT was collected; patients were grouped into 3 categories: nonsensitized (PRA &lt;10%), moderately sensitized (PRA 10-79%), and highly sensitized (PRA ≥80%). Data regarding crossmatch at HT were collected. One-year post-HT mortality based on sensitization category and crossmatch result were evaluated using multivariable Cox regression. Results: During the study period, 881 CHD patients with PRA data underwent HT; 69% nonsensitized, 22% moderately sensitized, and 9% highly sensitized. Positive crossmatch by flow cytometry or cytotoxicity was more commonly seen in highly sensitized patients (Table 1). Highly sensitized patients had 28% 1-year mortality. After adjustment, both 1-year mortality and graft loss were higher in highly sensitized patients than nonsensitized patients (HR 4, CI 2.4-6.7, P&lt;0.001 and HR 6.8, CI 3.6-12.8, P&lt;0.001, respectively); positive crossmatch by flow cytometry or cytotoxicity was also associated with increased risk of mortality and graft loss (HR 2.1, CI 1.3-3.4, P = 0.002 and HR 3.1, CI 1.7-5.6, P&lt;0.001, respectively). Conclusions: Highly sensitized pediatric CHD patients have 1-year post-HT mortality of nearly 30%, a 4-fold increase compared to nonsensitized patients; positive crossmatch also increased the risk of mortality and graft loss. Due to these poor outcomes, aggressive desensitization as well as alternatives to transplant should be considered in these high-risk patients.
Abstract 13510: Clinical Characteristics and In-Hospital Outcomes of Patients With Myocardial Infarction With Non-Obstructive Coronary Arteries in Japan -Lessons From the Real-World Database of JAMIR-
Authors: Sho Onuma, Jun Takahashi, Takashi Shiroto, Shigeo Godo, Kiyotaka Hao, Satoshi Honda, Nishihira Kensaku, Sunao Kojima, Misa Takegami, Tomonori Itoh, Masafumi Watanabe, Morimasa Takayama, Tetsuya Sumiyoshi, Kazuo Kimura, Satoshi Yasuda
Journal: Circulation (2023)

Background: A certain percentage of patients with acute myocardial infarction (AMI) do not have significant stenosis and they are termed as "myocardial infarction with nonobstructive coronary arteries (MINOCA)”. However, there were few studies representing MINOCA patients in the era of coronary intervention, in Asia in particular. Aims: We aimed to elucidate the clinical characteristics and in-hospital outcomes of patients with MINOCA in Japan by using a real-world database. Methods: The Japan Acute Myocardial Infarction Registry (JAMIR) is a nationwide, real-world multi-center registry study. We retrospectively analyzed 22,236 AMI patients (68±13 years, female 23.4%) enrolled in the JAMIR between 2011 and 2016. Results: Of those, 286 patients (1.3%) were diagnosed as MINOCA following coronary angiography and the remaining 21,950 patients (98.7%) were inevitably as myocardial infarction with obstructive coronary artery disease (MI-CAD). MINOCA patients were characterized by younger age, higher prevalence of women, fewer coronary risk factors, lower rate of ST-elevation AMI, lower Killip classes, and lower peak creatinine phosphokinase levels as compared to those with MI-CAD. In-hospital all-cause mortality was not different between MINOCA and MI-CAD groups (5.2% vs. 5.7%, P=0.82, OR adjusted by age and sex 1.06; 95%CI [0.63-1.80]), meanwhile non-cardiac mortality was significantly higher in the MINOCA group (4.2% vs. 1.6%, P&lt;0.01, adjusted OR 3.14; 95%CI [1.74-5.68]) ( Figure A ). Importantly, non-cardiac mortality increased with age in the MI-CAD group, whereas this did not apply in the MINOCA group ( Figure B ). Conclusions: The large-scale real-world database JAMIR demonstrated high prevalence of non-cardiac death in MINOCA, which indicate a clinical significance of comprehensive evaluations concerning underlying pathophysiological mechanisms of myocardial injury, especially in the younger patient group.
Abstract 15756: To Close or Not to Close: A Case of Multisystem Immune Checkpoint Inhibitor Toxicity and PFO
Authors: Ayesha Ropri, Jeanwoo Yoo, Mohammad El-Hajjar, Anuraag Sah, Boris Shkolnik, Dmitri Belov
Journal: Circulation (2023)

Introduction: Recent emergence of immune checkpoint inhibitors (ICIs) in oncologic treatments has led to increasing research on their side effect profile. Myocarditis occurs in roughly 0.04-1.14% of patients treated with ICIs and is associated with up to 50% mortality. We present a case of multisystem ICI toxicity requiring comprehensive evaluation to ultimately reveal a PFO shunt as the cause of persistent hypoxemia. Case: A 67-year-old male with Stage IIIC cutaneous melanoma presented with non-radiating pleuritic chest pain, diplopia, dyspnea and syncope. ECG showed high grade AV block and right bundle branch block. Labs showed elevated troponin, creatinine kinase and inflammatory markers. An echocardiogram showed edematous myocardium, a small pericardial effusion, and akinetic apical/inferior septal segments. Despite diuresis, 5g of methylprednisolone, IV immunoglobulin plus mycophenolate and resolution of AV block, the patient had hypoxemia on 100% FiO2. He underwent a CTA (which ruled out PE and ICI-induced pneumonitis) and fluoroscopic sniff test (revealing bilateral moderate diaphragm paresis). A recent cardiac catheterization on prior admission showed no obstructive coronary disease. Arterial blood gas showed pO2 120 mmHg without hypercapnia on 100% FiO2. We suspected a shunt as the underlying cause and obtained a bubble study disclosing a large (&gt; 25 bubble) PFO with right-to-left shunt. Results: Given the timing of symptoms, it was determined that pembrolizumab administration caused myocarditis and myositis with diaphragmatic paresis. In patients with pulmonary disease or diaphragmatic paresis, elevated intrathoracic and pulmonary artery pressures have been a proposed mechanism of acute worsening of right-to-left shunt resulting in hypoxemia. The patient underwent right heart catheterization and PFO closure using Gore Cardioform septal occluder with resolution of hypoxemia. A repeat echocardiogram obtained 1 month later was normal. Conclusion: All concerning clinical symptoms in the setting of ICI use require a thorough evaluation. In this case, persistent hypoxemia despite treatment for ICI toxicity unmasked a large PFO requiring closure. A multisystem approach should be used to assess suspected ICI myocarditis.
Abstract 16588: Electrophysiology Procedural Access and Growth in Remote Geographies Using Novel Remote Mapping and Clinical Support Software
Authors: Arun Mahtani, Bridget Lee, Brandon Doty, Jamarcus Brider, Arun Gopi, Devi Nair
Journal: Circulation (2023)

Introduction: COVID-19 redefined workflows in the field of electrophysiology (EP). The geographic paucity of experienced clinical mapping support was a crucial issue that limited the worldwide adoption of complex ablation procedures. Hypothesis: To ascertain the feasibility of utilizing a novel software for remote mapping and clinical support for all spectrums of cardiac ablation procedures in a remote geography. Methods: Ablation procedures performed at Metromed International Cardiac Centre (MICC); India were included in this early feasibility analysis (EFA). All procedures were performed by a single EP operator. Remote clinical support was provided by an EP physician (primary operator's sibling) in the US. Mapping was performed by an experienced mapper from a remote location 400 miles away from MICC. The mapping system utilized was Ensite Precision with SJM Connect software. Results: 360 contiguous ablation procedures from 2020 to 2023 were included in this EFA and compared to procedures performed between 2017 to 2019. The SJM Connect software allows remote access to the Ensite console via a secured connection. It requires the operator to be granted access to the console via a permission request. The software then allows the remote operator to access the system as view-only or complete control of the console providing full remote support. Communication occurs between the remote user and the console via a chat and voice call. There was an overall increase by three times in the total number of ablations performed after using the remote system. There was also an increase in different types of complex ablation procedures performed. Conclusions: This EFA demonstrates the safety and efficacy of using remote clinical support and mapping for ablation procedures. It opens a world of possibilities including the expansion of ablation technology to all corners of the world with experienced clinical mapping support connecting the EP community on a worldwide platform.