tbuckley/cabot-search huggingface dataset:
Abstract 19107: Variation in Women's Representation Among Leadership Positions in Pediatric Cardiology Programs Across North America
Authors: Alaina Kipps, Audrey Marshall, Ritu Sachdeva, Neha Bansal, Holly Bauser-Heaton, NADINE CHOUEITER, Devyani Chowdhury, Aarti Dalal, Molly S Ehlrich, Lindsay R Freud, Supriya Jain, Pei-Ni Jone, kristin laraja, Sonal Owens, Dalia Lopez-Colon, Christina Ronai, Corey Stiver, Nicole J Sutton, Jennifer Co-Vu
Journal: Circulation (2023)

Introduction: Despite several years of gender parity entering the field of pediatric cardiology, representation of women leaders trails that of their male colleagues. We sought to better understand the variation in women in leadership roles in our field. Methods: Pediatric cardiology programs that participate in the Society of Thoracic Surgeons database with &amp;gt 5 cardiologists were included. Data regarding gender of physicians in 16 leadership positions was collected. We analyzed the association of women in leadership roles with center size (based on surgical volume), geographic region, presence of fellowship, and gender of division chief and department chair. Results: Of the 99 centers in this study, a median of 13 (IQR 10-15) roles/center were identified, with 4 (IQR 3-6), 33.3% held by women. The lowest representation was in pediatric cardiology chiefs: 13% (table). Programs led by women chiefs had more women in leadership roles (48% vs 35%, p=0.01). In the US, the Northeast has more %women leaders than the West, South, or Midwest: 43% vs 33, 32, 34% respectively, p=0.035. Fellowship program or a woman department chair were not associated with %women leaders. The %women varied among the different sections: lowest in invasive subspecialties, interventional (17%) and EP (20%), and highest in fetal directors (66%). Fewer cardiac MRI leads in medium or high-volume centers are women compared to low volume centers (16 vs 39%, p=0.02), otherwise no volume-based differences were seen. Conclusions: Women hold fewer leadership positions across most subsections of pediatric cardiology programs, with more equitable distribution at centers led by women division chiefs. Future studies will define barriers to leadership equity.
Abstract 405: Characteristics and Care of Pediatric Out-of-Hospital Cardiac Arrest in the National Emergency Medical Services Information System
Authors: Chelsea B Kadish, Christopher Gage, Jonathan Powell, Alexander Ulintz, Henry E Wang, Ashish Panchal
Journal: Circulation (2023)

Background: Pediatric out-of-hospital cardiac arrest (OHCA) is an infrequent event with variations in clinical performance in the United States. Recent data on national incidence and treatments provided by Emergency Medical Services (EMS) clinicians during these events is unclear. We sought to characterize the incidence, medications, and procedures performed on children presenting with OHCA. Methods: We evaluated EMS responses in the US using 2021 National Emergency Medical Services Information System (NEMSIS) data. We included children (age ≥1 day - 17 years) with 9-1-1 responses. We identified OHCA events by those with reported: 1) cardiac arrest, 2) EMS resuscitation attempt, 3) EMS CPR performance, or 4) EMS defibrillation. We determined the incidence of pediatric out-of-hospital cardiac arrest among EMS responses and evaluated patient demographics (age, sex, race, location, urbanicity) and clinical interventions (medications, airway procedures). Results: Among 1.74 million pediatric 9-1-1 responses in 2021, we observed 13,040 OHCA events and an overall incidence of 7.6 per 1,000 pediatric 9-1-1 responses. For OHCA events, the median age was 3 years (IQR 0.33,14); 33% of events occurred in children less than one-year-old and 30% in adolescents aged 13-17. Most patients were male (58%) and events occurred mainly in urban settings (79%) and homes (63%). Of this population, 12% received defibrillation, 41% epinephrine, and 27% an advanced airway (endotracheal intubation or supraglottic airway). Conclusions: Pediatric OHCA incidence was low and followed a biphasic pattern by age. As expected in the pediatric population, defibrillation rates were low. One-quarter of patients received an advanced airway. Epinephrine, recommended for all cardiac arrests, was found to be administered in less than half of these events. Further studies are needed to evaluate barriers to optimal OHCA management in pediatric patients in prehospital settings.
Abstract 13112: Cardiovascular Complications During Delivery Hospitalizations in Patients With Pulmonary Hypertension: A Nationwide Analysis
Authors: Ankit Agrawal, Suryansh Bajaj, Umesh Bhagat, Sanya Chandna, Yasser Jamil, Muhammad Majid, Aro Daniela Arockiam, Mahmoud El, Erin D Michos
Journal: Circulation (2023)

Introduction: Pregnancy in patients with pulmonary hypertension (PH) is associated with a high risk of medical complications. We aimed to study the patient characteristics and association between PH and delivery complications. Hypothesis: PH is associated with poor outcomes in pregnant patients. Methods: We utilized the National Inpatient Sample (NIS) database 2011-2020 to identify adult patients (≥18 years) with PH undergoing delivery hospitalizations. The primary outcomes were in-hospital medical and obstetric complications. Multivariate regression was performed to study the association of PH with these complications. Results: A total of 37,482,207 delivery hospitalizations were identified out of which 9,593 patients had PH. Pregnant patients with PH had a higher incidence of complications at delivery like preeclampsia/eclampsia, cardiac arrhythmias, pulmonary edema amongst others as well as a higher incidence of in-hospital mortality compared to those without PH (0.51% vs 0.007%). In adjusted analyses, PH was independently associated with a higher risk of pulmonary edema (Odds ratio (OR) 18.65 (95% confidence interval (CI) 13.71-25.38), p&lt;0.001), peripartum cardiomyopathy (PPCM) (OR 14.06 (9.15-21.60), p&lt;0.001), venous thromboembolism (VTE) (OR 12.25 (7.80-19.24), p&lt;0.001), cardiac arrhythmias (OR 11.75 (10.11-13.67), p&lt;0.001), acute kidney injury (AKI) (OR 7.53 (5.36-10.58), p&lt;0.001), preeclampsia/eclampsia (OR 4.61 (4.04-5.25), p&lt;0.001), and acute coronary syndrome (ACS) (OR 2.83 (1.17-6.85), p=0.02), compared with pregnant patients without PH. Further, stroke (OR 127.33 (78.49-206.57), p&lt;0.001), AKI (OR 51.25 (34.40-76.36), p&lt;0.001), cardiac arrhythmias (OR 24.80 (19.43-31.65), p&lt;0.001), PPCM (OR 6.47 (3.23-12.97), p&lt;0.001), pulmonary edema (OR 4.27 (2.18-8.37), p&lt;0.001), VTE (OR 2.75 (1.07-7.10), p=0.036), and preeclampsia/eclampsia (OR 1.87 (1.35-2.60), p&lt;0.001) were associated with a high risk of in-hospital mortality in pregnant patients with PH as compared to those without PH. Conclusions: Delivery hospitalizations in patients with PH are associated with worse outcomes. Prenatal counseling and multidisciplinary care are essential to help mitigate unfavorable outcomes in this cohort.
Abstract 14967: Branching Out: Disrupted Branched Chain Amino Acid Metabolism Exacerbates Pulmonary Arterial Hypertension
Authors: Madelyn Blake, Sasha Z Prisco, Kurt W Prins
Journal: Circulation (2023)

Introduction: Valine, leucine, and isoleucine are essential branched chain amino acids (BCAA), and recent epidemiological studies report elevated BCAAs predict worse outcomes in several cardiovascular diseases with metabolic origins such as diabetes, heart failure, and hypertension. However, the role of BCAA metabolism in pulmonary arterial hypertension pathophysiology is relatively unexplored. Hypothesis: BCAAs are elevated in human PAH and reduction of BCAAs via small molecule activation of BCAA catabolism and dietary interventions combats PAH severity in preclinical PAH. Methods: Literature search of human PAH metabolomics studies was conducted. For rodent studies, male Sprague Dawley rats were divided into three groups: control (saline injection), monocrotaline (MCT) vehicle (MCT-V), or MCT-BT2, a small molecule inducer of BCAA catabolism. BT2 was administered at 20mg/kg/day. A low BCAA dietary intervention was implemented, with male Sprague Dawley rats divided into two groups: MCT-standard chow diet and MCT-low BCAA diet. To assess exercise capacity, rodents underwent a maximal exercise testing protocol before echocardiographic and hemodynamic assessments of PAH. Proteomic analysis of lung mitochondrial extracts was performed to define the molecular effects of BT2. Results: Of 11 studies evaluating human PAH metabolomics, 7 studies reported elevated BCAAs or BCAA metabolites in PAH. BT2 treatment improved exercise performance, reduced PA pressures, and augmented RV function. Moreover, the MCT-BT2 group possessed a distinct lung proteomic signature with changes in inflammatory and metabolic pathways. Finally, the low BCAA diet intervention modestly combatted PAH severity. Conclusions: BCAA metabolism is disrupted in human PAH and interventions that reduce circulating BCAAs display therapeutic potential in rodent PAH.
Abstract 16455: A Costly Mix-Up: Genotype-Phenotype Mismatch of Hereditary Transthyretin Cardiac Amyloidosis
Authors: Jemi Galani, Muling Lin, MATTHEW BROWN, Kunal Bhatt
Journal: Circulation (2023)

Introduction: Transthyretin cardiac amyloidosis (ATTR-CM) is an infiltrative process caused by the extracellular deposition of misfolded amyloid fibrils, resulting in a restrictive cardiomyopathy. Over 100 pathogenic genetic variants are associated with hereditary transthyretin cardiac amyloidosis (hATTR-CM); however, genetic penetrance is unknown. Typical echocardiographic findings include unexplained left ventricular (LV) hypertrophy - specifically concentric LV wall thickness greater than 12mm - and relative apical sparing of longitudinal LV strain. Cardiac MRI shows a characteristic diffuse subendocardial or transmural myocardial delayed gadolinium enhancement (DGE) pattern. Lastly, technetium-99m pyrophosphate scintigraphy (PYP) scan, an emerging sensitive and specific imaging modality, reveals grade 2 or greater myocardial uptake. Methods: We present a case series of three young patients, two who presented with new-onset, non-ischemic systolic heart failure, and one who presented with LV hypertrophy - suggestive of cardiac amyloidosis. Genetic testing and cardiac imaging with echocardiography, cardiac MRI and/or PYP scan were performed. Results: Genetic testing for all patients revealed the autosomal dominant and variably penetrant Valine 122 Isoleucine mutation, commonly associated with hATTR-CM. However, imaging for these patients was not suggestive of ATTR-CM. Therefore, they most likely represent silent carriers with alternate etiologies of heart failure. Discussion: This case series exemplifies several instances of genotype-phenotype mismatch in hATTR-CM. With the increasing use of genetic testing and the variable penetrance of this common pathogenic variant, a thorough evaluation must be conducted to ensure true cardiac infiltration in order to avoid inappropriately initiating the costly transthyretin stabilizer, Tafamidis, or disregarding alternative - potentially reversible - etiologies of heart failure.
Abstract 14921: Right Atrial Paraganglioma
Authors: Talha Bin Farooq, Vishesh Paul
Journal: Circulation (2023)

Introduction: Paragangliomas are rare tumors of neural crest cells origin and can be adrenal or extra-adrenal. They can be associated with catecholamine release in some patients and cause systemic symptoms. Cardiac paragangliomas account for less than 1% of all primary cardiac tumors. Case Summary: A 70-year-old woman presented to the emergency department with new-onset chest pain. Vitals were significant for elevated blood pressure but otherwise unremarkable. Physical exam and serum hematology and chemistries were unremarkable. D-Dimer was mildly elevated. Chest CT Angiogram showed a 1.5 cm right lung nodule but no pulmonary embolism. Outpatient Positron Emission Tomography (PET) scan done for further evaluation of the nodule showed no uptake in the lung nodule but a 5cm mass in the right atrium. Cardiac MRI confirmed the atrial mass with suspicion for angiosarcoma. The patient underwent surgery, and the pathology showed paraganglioma. Patient did well after the surgery. Discussion: Cardiac paragangliomas usually present with fatigue, atypical chest pain or heart failure. It can also present with signs of catecholamine excess. Surgery is the preferred treatment for benign paragangliomas. Surgery should be prompt as it has a potential to be malignant. Chemotherapy and radiolabeled agents are additionally used for the malignant types. Conclusions: There should be high clinical suspicion for secondary causes of hypertension in patients presenting with either episodic hypertension or resistant hypertension. Paragangliomas are very rare cardiac tumors and there have been very few reported cases of right atrial paraganglioma. Any suspicion of this rare tumor should prompt aggressive investigation and prompt referral to a center specializing in their removal.
Abstract 14475: Intrinsic T Cell Tolerance to the Autoantigen LL-37 is Mediated in Part by Platelets
Authors: Paul C Dimayuga, Xiaoning Zhao, Jianchang Zhou, Nicole W Lio, Fernando Chernomordik, Kuang-Yuh Chyu, Prediman K Shah, Bojan Cercek
Journal: Circulation (2023)

Introduction: An autoimmune response to human cathelicidin antimicrobial peptide LL-37, a component of neutrophil extracellular traps (NETs), may play a role in athero-thrombosis. We have reported that acute coronary syndrome (ACS) patients have increased LL-37 auto-reactive CD8+CD69+CD137+ T cells compared to healthy controls suggesting breach of tolerance to LL-37. Platelets present antigens to CD8+ T cells via HLA Class-I but it is unknown if this pathway is involved in maintaining intrinsic tolerance to the autoantigen LL-37. In this study, we investigated the role of platelets in maintaining immune tolerance to LL-37 in healthy subjects. Methods and Results: Platelets and autologous peripheral blood mononuclear cells (PBMCs) were isolated from remnant blood of platelet donor Leukocyte Reduction System cones from the institutional blood bank. Platelet enrichment was confirmed by CD41+ flow cytometry and over 95% were HLA Class-I(+). PBMCs were co-cultured with autologous platelets that were either non-primed or primed with LL-37 peptide at a ratio of 25:1 platelet-to-PBMC. Cells were collected after 16 hours and subjected to fluorescent staining for activation markers by flow cytometry. Compared to non-primed platelets, co-culture of LL-37-primed platelets significantly reduced T cell activation in autologous PBMCs including CD8+CD69+CD137+ T cells, CD4+CD134+ T cells and CD4+CD134+CD137+ T cells (Table), supporting platelet-mediated T cell tolerance to LL-37. We then evaluate if the breach in T cell tolerance to LL-37 in ACS is related to platelet counts. CD8+CD69+CD137+ T cell response to LL-37 in PBMCs of ACS patients was negatively correlated with platelet count (N=21; Pearson r = -0.438, P=0.047). Conclusions: The results demonstrate that intrinsic immune tolerance to the autoantigen LL-37 in healthy subjects is mediated in part by platelets. Reduced platelet counts are implicated in the breach of immune tolerance to LL-37 in ACS.
Abstract 14463: Beyond Sarcomere Mutations Plakophilin-2 and Familial Hypertrophic Cardiomyopathy
Authors: Shahrad Shadman, Leyla Gasimli-Gamache, Felicia Cabrera, Sarah Luther, Jamshid Shirani
Journal: Circulation (2023)

Background: Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous disorder with diverse clinical presentation, course and outcomes. It is commonly caused by mutations in sarcomeric genes. Non-sarcomeric gene mutations have been associated with HCM in certain metabolic and storage diseases. Pathogenic mutations in plakophilin-2 (PKP2) gene have been associated with enhanced desmosomal protein degradation and linked to arrhythmogenic right ventricular cardiomyopathy (ARVC), Brugada syndrome and dilated cardiomyopathy. We report an association between PKP2 gene mutation and familial HCM. Case presentation: A 65-year-old man with family history of HCM (maternal grandfather, 2 aunts and an uncle) presented with dyspnea on exertion (NYHA class II-III) and pedal edema. Echo showed severe LVH, mid-cavitary obstruction and LV apical aneurysm. Cardiac MRI confirmed findings (Figure:A and B) and additionally showed significant late gadolinium enhancement (Figure:C and D, &gt;20% of LV myocardium). Extended ambulatory heart monitor detected frequent runs on non-sustained ventricular tachycardia. A primary prevention ICD was implanted. Genetic testing identified a pathogenic mutation [c.1237C&gt;T (p.Arg413*)] in exon 5 of PKP2 gene resulting in premature translational stop signal and disrupted desmosomal protein plakophilin-2. Family screening (Figure:E) identified a sister with positive results who also had non-obstructive HCM (Figure:E). Discussion: We present a family with typical presentations of HCM and no phenotypic evidence of ARVC. This novel observation provides evidence for pleiotropic model of complex genotype-phenotype interactions through nonlinear networks. Further evidence would be needed to understand potential molecular basis of hypertrophic signaling in PKP2 gene mutation.
Abstract 17518: Aortic Dissection Repair of Both Stanford Type A and Stanford Type B Aortic Dissection in Teaching Hospitals is Associated With Lower Mortality
Authors: Renxi Li, Qianyun Luo, Derrick L Green, Stephen Huddleston
Journal: Circulation (2023)

Introduction: Aortic dissection (AD) repair is a high-risk procedure. Hospital teaching status may impact postoperative outcomes after AD repair. This study aimed to compare mortality after AD repair for both Stanford Type A (TAAD) and Stanford Type B (TBAD) in urban private practice (UPP) versus teaching hospitals (TH). Method: Patients who underwent TAAD and TBAD repair were identified in the National Inpatient Sample (NIS) from Q4 2015-2020 by ICD10-CM/PCS. Comparison of postoperative mortality between UPP versus TH among TAAD and TBAD were examined separately. In addition, mortality after open surgery and Thoracic Endovascular Aneurysm Repair (TEVAR) in TBAD were compared. Significant preoperative differences were present between cohorts, so multivariable logistic regressions were performed. Adjusted preoperative variables included sex, age, race, socioeconomic status, comorbidity, primary payer status, and hospital characteristics. Result: There were 316 patients in UPP and 4,494 patients in TH who underwent TAAD repair. In TBAD, 247 patients were treated in UPP and 3,845 patients were treated in TH. Of patients with TBAD, 114 UPP and 1,533 TH had open repair, whereas 133 UPP and 2,312 TH had TEVAR. Compared to TH, mortality was higher in both TAAD (aOR 1.37, p&lt;0.01) and TBAD (aOR 1.89, p&lt;0.01) in UPP. Within TBAD, UPP had higher mortality in both open repair (aOR 1.80, p&lt;0.02) and TEVAR (aOR 1.88, p&lt;0.05). At UPP, length of stay&gt;7 days was less common than in TH (aOR 0.50, p&lt;0.01) among patients who had TBAD open repair. Post-operative major adverse cardiac events, myocardial infarction, or stroke were not different in all AD groups when comparing patients in UPP to TH. Conclusion: Treatment of both TAAD and TBAD at UPP is associated with significantly higher in-hospital mortality. Emergent transfer to teaching hospitals might be considered to achieve lower mortality of AD.
Abstract 16164: Lipoprotein (a) Testing in Patients With Atherosclerotic Cardiovascular Disease in Five Large U.S. Health Systems
Authors: Nishant P Shah, Hillary Mulder, Betsy Lydon, Karen Chiswell, Zachary Lampron, Lauren Cohen, Adrian F Hernandez, Manesh R Patel, Susan Taubes, Wenliang Song, Suresh R Mulukutla, Anum Saeed, Daniel P Morin, Steven M Bradley, Xingdi Hu, Neha J Pagidipati
Journal: Circulation (2023)

Introduction: Lipoprotein (a) [Lp(a)] is an independent, causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Screening patterns remain variable and it is unclear what factors are associated with Lp(a) testing, and whether knowing the Lp(a) value changes management. Research Question: To better understand the proportion of Lp(a) testing, factors predicting Lp(a) testing, and impact on management in ASCVD patients. Methods: A retrospective study using electronic medical record data from five health systems in the CardioHealth Alliance and PCORnet® identified a cohort with an ASCVD diagnosis in 5 years prior to the index date. The index date was defined as the date of the first Lp(a) test result in 2019-2021 for those with a Lp(a) test, or the date of a randomly selected outpatient encounter in 2019-2021 for those without a Lp(a) test. Initiation of lipid lowering therapy (LLT) was assessed within 6 months after the index date. Multivariable regression modeling was used to determine factors associated with Lp(a) testing. Results: Among 595,685 ASCVD participants, only 2,588 (0.4%) were tested for Lp(a). In adjusted models, those who were older, Black, or Hispanic were less likely to have Lp(a) testing, while those with familial hypercholesterolemia, ischemic stroke/TIA, PAD, prior LLT, or LDL-C ≥130mg/dL were more likely to be tested (table). Those with elevated Lp(a) (&gt;50mg/dL or &gt;125 nmol/L) were more likely to initiate any LLT (43.9% vs 34.6%, p=0.03), particularly PCSK9i (10.9% vs 4.8%, p&lt;0.01) and ezetimibe (11.5% vs 5.9%, p &lt;0.01) compared to those without elevated Lp(a). Statin initiation remained similar between those with and without elevated Lp(a) (32.1% vs 29.5%, p=0.47). Conclusion: Lp(a) testing in ASCVD patients is infrequent, with evidence of disparities by race and ethnicity. Having elevated Lp(a) was associated with higher initiation of non-statin LLT. However, overall initiation of any LLT after an elevated Lp(a) test was low.
Abstract 17142: Deficiency of Smooth Muscle ADAR1 Exacerbates Vascular Remodeling and Pulmonary Hypertension
Authors: Yunhye Kim, Giovanni Maroli, Chen-Shan J Woodcock, Tim Klouda, Yuan Hao, Tiffany Liu, Valerie A Schumacher, Jin B Li, Benjamin Raby, Stephen Chan, Soni Pullamsetti, Ke Yuan
Journal: Circulation (2023)

Background: Adenosine deaminase acting on RNA 1 (ADAR1) catalyzes the conversion of adenosine (A) to inosine (I) in double-stranded RNA, which is critical to prevent auto-inflammatory responses mediated by activation of the type I interferon (IFN) signaling. Here, we define the role of ADAR1-dependent RNA editing in IFNβ activation and pulmonary artery smooth muscle cell (PASMC) remodeling in pulmonary arterial hypertension (PAH), a devastating disease leading to right heart failure and premature death. Methods: Total RNAs from IPAH PASMCs (N=3) and healthy control (N=3) were deep sequenced by RNA-seq and determined the fraction of reads with a ‘G’ nucleotide editing sites using RADAR database. A transgenic line ADAR1 SMC-KO was generated by knocking down ADAR1 selectively in αSMA+ cells, followed by 3 weeks of hypoxia. PKR inhibitor Imoxin was used to treat ADAR1 SMC-KO . Results: SMC layers of human IPAH tissues expressed reduced levels of ADAR1. Moreover, IPAH PASMCs displayed decreased mRNA and protein levels of ADAR1, along with reduced editing sites compared to healthy PASMCs (Fig.1A). The knockdown of ADAR1 in PASMCs resulted in the activation of the MDA5-PKR-IFNβ signaling pathway. Compared with controls in vivo , hypoxic ADAR1 SMC-KO mice developed severe PH, as evidenced by excessive vascular remodeling in distal arterioles (Fig.1B) and increased vascular leakage resulting in elevated right ventricular systolic pressure (37 vs 23 mmHg) and right ventricular hypertrophy by Fulton Index (46 vs. control 20%) (Fig.1C). The immunofluorescence staining showed higher expression of IFNβ and increased recruitment of inflammatory immune cells. Imoxin treatment prevented PH &amp; RVH. Conclusions: The deficiency of ADAR1 leads to the activation of IFNβ thus contributing to the pathological processes observed in PAH. Inhibiting PKR activity could attenuate the aberrant IFNβ activation and potentially serve as a new therapeutic strategy to treat PAH.