tbuckley/cabot-search huggingface dataset:
Abstract 17376: Comprehensive Quantitation of Cardiac Tissue Derived Extracellular Vesicles Regulating Adipose Tissue Metabolism
Authors: Jennifer L Pennise, Antonia Yuko, Daria Harlamova, Sadia Mohsin, Fabio A Recchia, Mohsin Khan
Journal: Circulation (2023)

The heart is considered as a recipient of signals from the periphery to fine tune blood pumping in response to physiological and pathological changes. Cardiac secretory function consisting of proteins termed as cardiomyokines has founded the concept of heart mediated organ crosstalk . Studies have shown extracellular vesicles (EVs) are major players regulating organ crosstalk between peripheral organs and the heart. Nevertheless, whether cardiac tissue derived EVs with unique composition deliver messages to peripheral organs remains unknown. Paired serum samples isolated from coronary sinus (CS) and aorta (AO) of dogs under normal and tachypacing induced heart failure were used for EV isolation, characterization and miRNA array analysis. Transplantation of EV from CS and AO samples under normal and heart failure conditions in wild type mice was done to determine whole body metabolism by CLAMs and modulation of adipose tissue metabolism together with in vitro functional assay in cultured adipocytes. Results showed heart failure promotes increased secretion of EVs in the CS compared to AO blood suggesting heart produces more EVs under diseased conditions. miRNAs array analysis identified top elevated miRNAs as miRNAs 16, 92 and 137 significantly enriches in CS EVs under heart failure conditions. Measurement of miRNAs 16, 92, 137 is different tissues showed significantly increased expression in brown adipose tissue (BAT) compared to all other tissues assessed. Next, 3TC-LI adipocytes treated with CS EVs from heart failure dogs showed decreased OXPHOS measured by Seahorse, reduced expression of mitochondrial markers and low BODIPY labelling together with increase in whole body oxygen consumption rates, food intake and energy expenditure as measured by CLAMS. Mechanistically, EV derived miRNAs 16, 92, 137 significant transcriptomic changes BAT assessed by bulk RNA-sequencing. Top altered genes identified in BAT were UQCR10, CPT1a and PGC1a after administration of CS EVs from heart failure animals and are binding targets for miRNAs 16, 92 and 137 respectively. In conclusion, cardiac tissue communicates to adipose tissue to regulate metabolism by releasing EVs derived miRNAs enriched differently in response to heart failure or under normal conditions.
Abstract 19053: Peripheral Eosinophil Count is Associated With Left Ventricular Systolic Dysfunction During Spontaneous Coronary Artery Dissection
Authors: Bianca J Lavelle, Anna Pawlowski, Matthew J Feinstein
Journal: Circulation (2023)

Background: Spontaneous coronary artery dissection (SCAD) is an underdiagnosed condition disproportionally affecting young women, particularly during the peripartum period and/or in the presence of systemic inflammatory and autoimmune diseases. Tissue-level studies have demonstrated inflammatory infiltrates with adventitial or peri-adventitial eosinophilia at the site of SCAD lesions. Less is known regarding how systemic markers of immune activation associate with cardiac dysfunction in SCAD. Hypotheses: Higher eosinophil count and Neutrophil-to-Lymphocyte Ratio (NLR) associate with LV systolic dysfunction in SCAD patients. Methods: In individuals diagnosed with SCAD who underwent CBC with differential and echocardiography within the same presenting hospital encounter, we performed age- and sex-adjusted logistic regressions with eosinophil count (% of differential) and NLR (% of differential) as primary exposures and LVEF&lt;55% as the dichotomous endpoint. A p&lt;0.05 was considered statistically significant. We explored associations of neutrophil, lymphocyte, monocyte, and basophil counts with LVEF in secondary analyses. Results: In SCAD patients with complete CBC and LVEF data (N=36; mean age 49.9 years at diagnosis, 28 female), peripheral eosinophil count was associated with significantly higher odds of systolic dysfunction [OR of LVEF&lt;55% per every 1% higher eosinophil count = 1.87; 95% CI 1.04, 3.36; p=0.04]. NLR ratio was not associated with LV systolic dysfunction (OR 1.05; 95% CI 0.94, 1.18; p=0.35) nor were other circulating leukocyte fractions. Conclusion: Peripheral eosinophil count, but not other circulating leukocyte counts, was associated with LV systolic dysfunction as measured by LVEF &lt;55%. These findings provide complementary support to pathology-based evidence of eosinophilia observed in SCAD lesions and require confirmation in future longitudinal studies of changes in LV function following SCAD events.
Abstract 19056: Tailoring Strategies to Improve Implementation of a Heart Failure Admission Decision Aid: A Qualitative Study
Authors: Maria A Alvarenga, Stacy L Farr, Katherine A Vilain, Danielle Olds, Raul Angel Garcia, Vittal Hejjaji, John A Spertus
Journal: Circulation (2023)

Introduction: High variability in heart failure (HF) readmissions persists despite national efforts and incentives. A standardized care path, CodeHF, was developed for use in the emergency department (ED) to better identify HF patients warranting admission. CodeHF was implemented in Kansas City in 2018. Despite positive patient and hospital-level outcomes, use of CodeHF has lagged. Hypothesis: A qualitative study was conducted to understand barriers and facilitators behind the implementation of CodeHF with the goal of tailoring strategies to increase usage and scalability to other hospitals. Methods: Semi-structured interview guides were developed based on the Tailored Implementation in Chronic Diseases (TICD) list. 21 stakeholder interviews were conducted and thematic coding of interview transcripts was performed. Codes were matched to a relevant TICD determinant and implementation strategy from the Expert Recommendation for Implementing Change project. A tailored recommendation was created for each strategy. Results: Analyses revealed 10 key themes: 1) Quality of Evidence: Skepticism of evidence; 2) Liability: Concern of CodeHF use in litigation; 3) Technical Difficulties: Challenges and errors during roll-out; 4) Ownership: Lack of ED ownership and champions; 5) Buy-In: Lack of ED buy-in due to the external project origin; 6) Understanding of Tool: Confusion of purpose and intended users; 7) Utility of Tool: Doubts of value in practice; 8) Exceptions to pathway: Concerns about inappropriate use; 9) Admitting Physician Awareness: Lack of recognition of CodeHF by admitting physicians; 10) Follow-up: Appreciation for rapid follow-up for discharged patients. Conclusions: Despite evidence supporting the positive impact of CodeHF, several implementation barriers and few facilitators were identified. Presenting updated evidence, partnering with new champions, educating providers on clinical and legally protective benefits, spreading awareness about technical solutions, inviting ED providers to lead redesign/relaunch, encouraging initial and ongoing educational meetings at all levels, emphasizing the follow-up benefit, and educating cardiologists and hospitalists are potential strategies for overcoming these barriers.
Abstract 17276: NOTCH3-BMPR Interactions Drive Smooth Muscle Cell Proliferation and Medial Hyperplasia in Pulmonary Arterial Hypertension
Authors: Yu Zhang, Cristian Puerta, Moises Hernandez, Patricia Thistlethwaite
Journal: Circulation (2023)

Background: One of the characteristics of pulmonary arterial hypertension (PAH) is the proliferation of smooth muscle cells. In heritable PAH, aberrant BMPR2 signaling results in low levels of intracellular ID1. An important pathway involved in vascular smooth muscle cell proliferation and the development of non-heritable PAH is the NOTCH3-HES5 signaling pathway. Previous studies have demonstrated that HES-5 and ID-1 are peptides belonging to the basic helix-loop-helix family, and they act as transcriptional enhancers of cell cycle genes. Transcriptional enhancement or repression requires the heterodimerization of different HES and ID proteins. Hypothesis: We hypothesize that HES-5 binds to and degrades IDs in non-heritable cases of PAH. Methods: The half-life of ID proteins was assessed in human small pulmonary artery smooth muscle cells that either constitutively expressed or minimally expressed HES-5. In order to understand whether this effect was due to direct binding between HES-5 and ID1, co-immunoprecipitation experiments were performed. Immunofluorescent staining was used to detect the expression level of ID1 and HES-5. Proximity ligation assay (PLA) was utilized to examine of endogenous in-situ interaction of ID1-HES5. Results: We found that overexpression of HES-5 significantly diminished the half-life of ID1 and ID3, and had little effect on ID2. All three proteins localized to the nucleus of small pulmonary artery smooth muscle cells. Immunofluorescent staining confirmed elevated levels of HES and reduced levels of ID1 and ID3 in the medial layer of PAH vessels. By PLA assay, we show that HES-5 and ID1 as well as HES-5 and ID-3 physically associate with each other to the level of 40 nanometers. Conclusions: Constitutive NOTCH3 signaling and high intracellular HES-5 levels drive vascular smooth muscle cell proliferation in non-familial PAH by binding to and degrading ID intracellular proteins. Our study demonstrates cross-talk between the NOTCH3-pathway and the BMPR2 pathway in this disease, at the level of their downstream effectors: ID1 and HES-5. Further studies should shed light on how these two pathways control the PAH disease process.
Abstract 17346: The Causal Role of Obstructive Sleep Apnea (OSA) in Atrial Fibrillation (AF): A Systematic Review and Meta-Analysis of Mendelian Randomization Studies
Authors: Ayodya Perera, Subramanian Gnanaguruparan, Athri Kodali, Venkata Balaji Chenna, Vaidehi Mendpara, BONEY LAPSIWALA, Pratik Bharat Rajpopat, Rohini Bhuvaneshwari Gurumoorthy, Amritha Nair, Brinda Desai, Valeriia Iermolenko, Avilash Mondal, Rupak Desai
Journal: Circulation (2023)

Background: Atrial fibrillation (AF) causes significant morbidity and mortality. Obstructive sleep apnea (OSA) has been suggested as a risk factor for AF, but the causal relationship between the two is still being investigated. We performed a systematic review and meta-analysis of Mendelian Randomization (MR) studies to determine OSA's role in AF. Methods: We searched PubMed, Scopus, Embase, and Google Scholar databases for MR studies on the causal relationship between OSA and AF through June 2023. Our analysis included eligible studies. The pooled odds ratio and subgroup analysis were calculated using the random-effects model. The I2 statistic was used to assess study heterogeneity, and a leave-one-out sensitivity analysis was performed to determine how individual studies affected the overall estimate and analysis robustness. Results: 5 MR studies met our inclusion criteria until June 2023. In these studies, one used diverse datasets and included patient data of 5 cohorts with UK, Canada, Australia, USA, Finland ancestry while the remaining 4 included patient data of European ancestry. Genetic predisposition to OSA was found to cause AF in the pooled odds ratio analysis (OR 1.21, 95% CI 1.15-1.28, I2=0.00%, p &lt;0.01). The leave-one-out sensitivity analysis showed that the odds ratio marginally changed when specific studies were excluded, suggesting that their contribution to the estimate slightly differed. Conclusion: Our findings suggest a causal relationship between OSA and AF, suggesting that OSA may cause AF. The findings emphasize the need for early evaluation and treatment of AF patients with OSA. However, large-scale prospective studies are required to confirm these findings and determine their clinical practice implications.
Abstract 17381: Relationship Between Amaurosis Fugax and Intraplaque Hemorrhage in Patient With Carotid Plaques
Authors: Karlo A Wiley, Allison Anker, Cristina Sanina, Guliz Kozdag Gold
Journal: Circulation (2023)

Introduction: The term amaurosis fugax is often used interchangeably to describe transient visual loss. However, it is employed widely in medicine to refer to any cause of transient monocular visual loss. Amaurosis fugax is associated with an imminent stroke and it could be linked to vascular thromboembolic events arising from the internal carotid arterial system. The aims of the study are to determine the plaque characteristics of patients who underwent carotid artery revascularization and the relationship of plaque characteristics with amaurosis fugax. Methods: Before elective carotid revascularization 44 patients (mean age 72±8 years; 25 males, 19 females) underwent 3-T MRI. After localization of the carotid bifurcation using phase contrast imaging, Time-of-Flight, 3D T1 weighting, transverse T1 and T2 weightings and proton density sequences were acquired. The different plaque components: lipid rich core, intraplaque hemorrhage, calcification and the characterization of the fibrous cap were assessed. Results: Carotid plaque samples had the following characteristics: Intraplaque hemorrhage (59%), surface defects (38.6%), stable fibrous cap (27.3%), lipid rich necrotic core (18%), and calcifications (11.4%). Amaurosis fugax history was identified in 7 patients (15.9%). Plaque samples from all 7 patients who had experienced amaurosis fugax revealed intraplaque hemorrhage. MRI revealed intraplaque hemorrhage in 19 (51%) patients without history of amaurosis fugax (p=0.016). The rest of the plaque characteristics did not show any statistically significant relationship with history of amaurosis fugax. Conclusions: This study demonstrated that intraplaque hemorrhage may be correlated to amaurosis fugax.
Abstract 17222: Warriors Takotsubo Syndrome
Authors: Lauren E Druml, Xinge Hu
Journal: Circulation (2023)

Background: Takotsubo syndrome (TTS), also known as stress-induced cardiomyopathy or "broken heart syndrome," is characterized by transient left ventricular dysfunction, typically triggered by negative emotions or physical stressors. It presents with symptoms similar to acute coronary syndrome, but with no associated coronary artery stenosis. “Happy Takotsubo” syndrome, triggered by intense positive emotions, is an uncommon variant and presents a unique challenge in clinical diagnosis. Case Presentation: An 86-year-old woman who was an avid Golden State Warriors fan developed sudden-onset pressure-like chest pain following intense excitement over the Golden State Warriors winning a critical basketball game. In the emergency department, the patient was found to have a high sensitivity troponin greater than 4,000 and ST elevations in leads V3 to V6, meeting STEMI criteria. Emergent cardiac catheterization revealed no coronary artery stenosis. Echocardiography was significant for apical ballooning of the left ventricle, consistent with TTS (Figure 1). Symptoms resolved following low-dose beta-blocker therapy, and the patient was discharged after 24 hours of observation. Repeat echocardiography eleven days later demonstrated near-resolution of the apical ballooning (Figure 2). Discussion: This case highlights "happy Takotsubo" syndrome as a unique presentation of TTS triggered by intense positive emotions. In this case, the patient developed TTS after experiencing excitement over a Golden State Warriors victory. By sharing this case, we aim to contribute to the existing literature and enhance knowledge about this uncommon presentation.
Abstract 17323: Avoiding Procedural Closure of the Patent Ductus Arteriosus Following Late Acetaminophen Therapy in Preterm Infants
Authors: Sarah Dudley, Craig Wheeler, Sarah U Morton, Zahara Khazal, Kaylyn Mitchell, Elyssa Horn, kimberly chamberlain, Kevin G Friedman, Michael Farias, Diego Porras, Philip T Levy
Journal: Circulation (2023)

Introduction: Management of a hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants beyond 3 weeks of age continues to be a debate. Clinical equipoise exists between pharmacologic agents versus procedural closure techniques (surgical ligation or transcatheter occlusion). The efficacy of acetaminophen for early closure of hsPDA has been demonstrated, but there remains a paucity of data for late closure. Hypothesis: To test the hypothesis that late administration of acetaminophen for a hsPDA is associated with reduced rates of procedural closure in preterm infants. Methods: We performed a post-hoc analysis of preterm infants (&lt;37 weeks) referred to Boston Children’s Hospital for ongoing management of a hsPDA from January 2019 to January 2023. We compared neonates with a hsPDA exposed and not exposed to acetaminophen at &gt; 3 weeks of age. The primary outcome was avoidance of procedural closure. We assessed for predictors of closure following acetaminophen therapy. Results: We identified 110 preterm infants (median gestational age of 25 weeks at birth) referred for closure of a hsPDA beyond 3 weeks of age (Fig). Late acetaminophen was used in 26 patients (median postnatal age of 31 days). Late acetaminophen was associated with higher rates of non-procedural PDA closure 10/26 (38%), compared to 6/84 (7%) of infants who did not receive late acetaminophen (OR 0.12, CI 0.04 - 0.39, p &lt; 0.01). Presence of flow reversal in the descending aorta was associated with lower likelihood of PDA closure with late acetaminophen (OR 0.09, CI 0.01 - 0.85, p=0.017). Conclusions: This study found that preterm infants with a hsPDA treated with late acetaminophen had a decreased need for procedural closure. Infants who responded were less likely to have flow reversal in the descending aorta, suggesting that consideration of a course of late acetaminophen prior to procedural closure of a hsPDA in preterm neonates should be selective and based on patient-specific risk factors.
Abstract 16878: Exercise Intolerance in Heart Failure With Preserved Ejection Fraction is More Closely Related to Energetic Decline During Exercise Than to Mitochondrial Oxidative Capacity in Recovery
Authors: T. Jake Samuel, Sabra Lewsey, Michael Schaer, Kilian Weiss, Angela M Steinberg, Joevin Sourdon, Paul A Bottomley, Gary Gerstenblith, Robert G Weiss
Journal: Circulation (2023)

Introduction: Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with severe exercise intolerance (EI) and exertional fatigue. Impaired skeletal muscle high-energy phosphate metabolism has been reported in HFpEF patients and postulated as a potential contributor to EI. However, whether EI is more closely related to rapid energetic decline during exercise, or reduced mitochondrial oxidative capacity remains unknown. Hypothesis: We hypothesized that six-minute walk distance (6MWD) is more closely related to the rate of skeletal muscle energetic decline during exercise than mitochondrial oxidative capacity in HFpEF. Methods: Calf muscle energetics were measured by phosphorus magnetic resonance spectroscopy ( 31 PMRS). The rate of phosphocreatine (PCr) decline normalized to work performed during graded plantar flexion exercise to volitional fatigue and the time for PCr post-exercise recovery, an established metric inversely related to mitochondrial oxidative capacity, were measured in 64 HFpEF patients (age: 65 ± 11 years; 53% women). Results: The mean rate of PCr decline, PCr recovery time, and 6MWD were 52 ± 108 μmol/g wet weight/KJ, 80 ± 45 seconds, and 296 ± 109 meters, respectively. The 6MWD was inversely related to the rate of PCr decline (r = -0.46; P = 0.0002; Figure, A ) but not significantly related to the PCr recovery time (r = -0.06; P = 0.66; Figure, B ), as determined by Pearson’s correlation coefficients. Conclusions: EI, as measured by 6MWD, in HFpEF patients is closely associated with impaired skeletal muscle metabolism, specifically rapid skeletal muscle PCr decline during exercise rather than mitochondrial oxidative capacity. This suggests that impaired glycolytic metabolism and substrate delivery may contribute metabolically to EI in HFpEF patients.
Abstract 19087: Cardiac Magnetic Resonance Imaging Increased Utilization of Cardiac Treatment in Young Duchenne Muscular Dystrophy Patients
Authors: Kan N Hor
Journal: Circulation (2023)

Introduction: Duchenne muscular dystrophy (DMD), an X-linked recessive disorder affecting up to 1 in 6000. DMD-associated cardiomyopathy (DMD-C) is universal and starts as young as 6 years of age by cardiac magnetic resonance imaging (CMR) with presence of late gadolinium enhancement (LGE). Heart failure signs and symptoms are vague due to skeletal muscle myopathy. Echocardiogram only detects global dysfunction by left ventricular ejection fraction (LVEF) which rarely occur before 10 years of age. The current DMD cardiac care consideration guidelines (CCCG) recommends initiation of cardiac medication around 10 years of age or if there is LGE and/or LVEF abnormalities . Hypothesis: We hypothesized young DMD were more likely to have cardiac therapy initiated after CMR compared to only TTE evaluation. Methods: Electronic medical records for DMD patients (6 to &lt; 10 years) who underwent routine TTE or CMR evaluation between 2014-2023 were included. Demographic data at the time of the study and initiation of cardiac medication including angiotensin-converting-enzyme inhibitor (ACE-I), Angiotensin II receptor blockers (ARB) and/or Mineralocorticoid Receptor Antagonists (MRA) were recorded. Results: 150 patients met inclusion criteria, of these 81 patients underwent TTE only and 69 underwent CMR evaluation in lieu of TTE with no difference in age (8.4±1.1 versus 8.6±0.8 years, P = 0.07). Of those with TTE evaluation 10/81 (12.3%) was initiated with ACE-I or ARB ( 3/10 (33%) had LVEF &lt; 55% (average 53.5%), 4/10 (40%) turned 10 on the follow-up visit and 3/10 (30%)) because family requested. Of the 69 patients with CMR, 51/69 (73.9%) had cardiac therapy initiated (28/51 (54.9%) because of new LGE, 6/51 (11.8%) due to isolated LVEF &lt; 55% (average 53%), 12/51 (23.5%) would turn 10 on follow-up and 5/51 (9.8%)) the family requested. All patients with LGE on CMR also had MRA therapy started. Conclusions: DMC-C is universal and the use of CMR improved disease specific treatment of both ACE-I/ARB and MRA. Duboc et al, in a placebo control study showed that in 9.5 - 13.5 year old DMD patients treated with ACE-I had fewer patients develop dysfunction with reduced mortality at 10 years. Early and aggressive treatment may attenuate DMD-C. Future longitudinal study is needed.