tbuckley/cabot-search huggingface dataset:
Abstract 4146431: Acute Brain Attack: Peering Through The Esophageal Window In Cryptogenic Ischemic Stroke
Authors: Santiago Galeano, Demilade Adedinsewo, Richard White
Journal: Circulation (2024)

The growing adoption of advanced imaging modalities, such as transesophageal echocardiography (TEE), has led to more frequent detection of cardiac structural abnormalities. While intracardiac cardiac tumors and shunts are infrequent and typically asymptomatic, their existence can precipitate severe outcomes, including stroke, myocardial infarction and sudden death. Case Description: A 69-year-old female presented with left sided facial droop, slurred speech and left arm weakness. A computed tomography angiography revealed focal occlusion of the distal right middle cerebral artery. She was initiated on thrombolytic therapy and experienced resolution of symptoms. Transthoracic echocardiogram revealed right to left shunting consistent with a patent foramen ovale (PFO). Further workup with TEE confirmed the presence of a PFO but also detected a mobile echogenic mass on the aortic valve leaflet, indicative of papillary fibroelastoma (PFE). Cerebral infarction was attributed to an embolic event, with the PFO and PFE being likely culprits. Discussion: Current guidelines give a conditional recommendation, low certainty of evidence, for PFO closure in adults older than 60 years, although some observational studies have shown some risk reduction in older patients. The key trials showing clinical benefit of PFO closure were in adults younger than the age of 60. For left sided cardiac tumors, such as PFE, guidelines give a 2A recommendation for resection. Addressing the risk for recurrent stroke in this 69-year-old patient was an essential part of stroke care, as such, a multi-disciplinary team of experts including cardiology, neurology, and cardiothoracic surgery was conveyed. The decision was to proceed with surgical intervention in addition to antiplatelet therapy to achieve optimal risk reduction. The patient subsequently underwent successful surgical removal of the PFE with native valve preservation and PFO closure. Conclusion: Cardiac PFEs and PFOs can be associated with increased stroke risk. Employing appropriate imaging techniques and timely interventions are of utmost importance in stroke management.
Abstract 4146277: Risk and Predictors of Hemorrhagic Complications in Extracorporeal Cardiopulmonary Resuscitation Patients: Insights from the SAVE-J 2 Registry
Authors: Madoka Sano, Toshiaki Toyota, Yoshinori Matsuoka, Yusuke Watanabe, Hirohiko Kohjitani, Yuta Azumi, Hideyuki Hayashi, Ryosuke Murai, Junichi Ooka, Yasuhiro Sasaki, Tomohiko Taniguchi, Kitae Kim, Atsushi Kobori, Natsuhiko Ehara, Makoto Kinoshita, Yutaka Furukawa
Journal: Circulation (2024)

Introduction: Extracorporeal cardiopulmonary resuscitation (E-CPR) is an emerging resuscitative therapy for patients with refractory cardiac arrests with various underlying conditions. However, hemorrhagic complications remain a significant challenge, adversely affecting patient outcomes. Research Questions: Risks and predictors of hemorrhagic complications in E-CPR patients may differ based on the causes of cardiac arrest. Aims: To compare the risks and predictors of hemorrhagic complications among the groups with different causes of cardiac arrest in patients undergoing E-CPR. Methods: The SAVE-J 2 registry is a multicenter registry of patients who underwent E-CPR for out-of-hospital cardiac arrest (OHCA) from 2013 to 2018. The patients were stratified into three groups based on the underlying causes of OHCA: endogenous cardiac, endogenous non-cardiac, and exogenous. The primary outcome was any bleeding, whereas the secondary outcomes included bleeding at cannulation sites and non-cannulation site bleeding. Pre-specified covariates were evaluated using the Cox proportional hazards model to identify the independent risk factors for bleeding. Results: Of the 2,070 patients who underwent E-CPR, 1,498 had endogenous cardiac causes, 344 had endogenous non-cardiac causes, and 228 had exogenous causes. The median follow-up among survivors was 35 days (interquartile range [IQR]: 21-55 days). Most of the bleeding events occurred within a week after E-CPR (median two days, [IQR: 1-8 days]). The 30-day cumulative incidence of any bleeding was significantly different among the three groups (endogenous-cardiac: 342 [26.1%]; endogenous-noncardiac: 47 [18.9%] and exogenous: 31 [15.1%], P&lt;0.001). There was also significant difference among the three groups regarding puncture-related bleeding and non-puncture site bleeding (Figure). Multivariable analysis suggested that the potential risk-estimating variables for bleeding were different among the three groups. Conclusions: Hemorrhagic complication risks and predictors vary depending on causes of cardiac arrest in E-CPR patients. These findings highlight the need for individualized management strategies to mitigate bleeding risks and improve outcomes.
Abstract 4146476: Clinical and CT morphological features versus CT texture analysis in identification of primary pulmonary artery sarcoma and central pulmonary embolism
Authors: Jingxi Wang, Chenyue Liu
Journal: Circulation (2024)

Research Queation: To evaluate clinical and CT morphological features versus CT texture analysis in differentiating primary pulmonary artery sarcoma (PAS) and central pulmonary embolism (PE). Methods: 23 pathology-proven primary PAS patients and 54 pathology-proven central PE patients from September 2013 to September 2023 were continuously enrolled. Clinical features and qualitative CT pulmonary artery (CTPA) morphological features were retrospectively collected. The chi-square tests or Mann–Whitney U test was applied to find the significant features. Then the discriminative features were identified by univariate logistic analysis. The CTPA texture features were extracted using a radiomics software (Radiomics, Syngo.Via FRONTIER, version 1.4.0; Siemens). Minimum redundancy and maximum relevance (MRMR) method was used to select significant texture features. A clinical model and a texture model for distinguishing primary PAS from central PE were built using multivariate logistic regression. The performance of two models was assessed using the area under the curve (AUC). Results: 10 from 1226 texture features selected by MRMR showed good performance in discriminating between the two groups (AUC &gt; 0.80), of which 5 were chosen to build the texture model using multivariate logistic regression. These features were wavelet_LLL_glrlm_ShortRunHighGrayLevelEmphasis, wavelet_LHH_glszm_LargeAreaEmphasis, exponential_glszm_GrayLevelNonUniformity, original_glcm_Imc1 and wavelet_HLH_firstorder_Mean, respectively. Univariate logistic analysis was used to find 18 discriminative (p &lt; 0.05) features, of which 4 were selected to build the clinical model using multivariate logistic regression. These features were lower limb edema, involvement of main pulmonary artery, involvement of pulmonary valve or right ventricular outflow tract and expansive growth in peripheral pulmonary artery. We evaluated these two prediction models based on CT textural features and clinical plus qualitative CTPA morphological features. These two models both showed high predictive accuracy. AUC of CT textural features model and clinical plus qualitative CTPA morphological features model were 0.97 (0.90 - 0.99) and 0.93 (0.85 - 0.98) respectively (p=0.36). Conclusion: We found very effective clinical and CTPA morphological features for the differential diagnosis of PAS and central PE, while CT texture analysis can additionally provide accurate, objective and quantitative diagnostic information.
Abstract 4146491: Impact of marathon running on cholesterol transfer to high-density lipoprotein in individuals with and without dyslipidemia.
Authors: Thaiz Carolina Pimentel Colognese, Fatima Freitas, FABIANA HANNA RACHED, Carlos Serrano, Anatol Kontush, Raul Maranhao, Pedro Senger, Roberta Vanalli Baroni, Eduardo Lima, Thauany Tavoni
Journal: Circulation (2024)

Introduction: Exercise training is known to improve cardiovascular risk, to increase HDL cholesterol (HDL-C) levels and HDL functionality, by improvement of cholesterol uptake by HDL, and decreases the potential atherosclerotic of low-density lipoprotein (LDL) particles. Marathon running is presumed to have the same effects, however health benefits of high volume running in dyslipidemic marathon runners are unknown. Aims: Using marathon runners as models for intense exercise training, this study aimed to evaluate differences in HDL composition, function and vascular reactivity between marathons runners with and without dyslipidemia, comparing with sedentary controls. Methods: 20 marathon runners with and 13 without dyslipidemia, 17 sedentary individuals with and 12 without dyslipidemia were enrolled. In all individuals, plasma lipids and apolipoproteins (apo) were measured by commercial kits and HDL size by laser light scattering method. Paraoxonase 1 (PON1) activity using commercial kits and vascular reactivity were evaluated. Lipid transfer was performed by incubating plasma with a lipid donor nanoemulsion containing radioactively labeled non-esterified cholesterol (NEC) and esterified cholesterol (EC), followed by chemical precipitation and radioactive count. We also performed an assay that analyses the cholesterol transfer to HDL from TGRL upon lipolysis. Results: All individuals were male, with no age difference between groups (42 to 47 years). Marathon runners without dyslipidemia were thinner than the other groups. While HDL-C concentrations and apo A1 levels were higher in runners, LDL-C and apo B levels were higher in dyslipidemic groups. Regarding PON1 and vascular reactivity, no statistical differences were observed. We observed greater transfer of EC and NEC in the marathon runners compared to sedentary individuals (p 0.015), with no difference between marathon runners with and without dyslipidemia. Important correlations were observed between Apo A1 and all transfers: both NEC and EC, and also cholesterol transfer to HDL from triglyceride-rich lipoprotein (TGRL) upon lipolysis (p &lt; 0.001, &lt;0.001 and 0.011, respectively). Additionally, we observed correlation between ApoA1 and vascular reactivity (p=0.032). Conclusion: Marathon runners have higher levels of HDL-C and apo A1. They have a better ability to cholesterol transfer to HDL and this functionality remains despite being dyslipidemic, with increased levels of LDL-c and apo B.
Abstract 4146330: Circular-RNA telomerase reverses endothelial senescence
Authors: Weifeng Qin, John Cooke, Anahita Mojiri, Daniel Kiss, Kathrina Castillo
Journal: Circulation (2024)

Background: Hutchinson-Gilford Progeria Syndrome (HGPS) is caused by a mutation in LaminA (progerin), and is characterized by accelerated aging and death from coronary or carotid disease in the mid-teens. We have shown that vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) derived from HGPS children manifest many of the hallmarks of aging including telomere erosion, reduced proliferation, impaired function, DNA damage and senescence markers, altered cellular and nuclear morphology, and an aberrant transcriptional profile. These hallmarks of aging are substantially reversed by treatment with telomerase (hTERT) linear RNA,with greater benefit in HGPS cells than the current therapy, lonafarnib. However, linear RNA has a short half-life, which necessitates frequent administration. By contrast, circular (circ) RNA is more stable than linear RNA, and with an internal ribosome entry site can be translated into protein. We hypothesized the hTERT circRNA would provide for longer duration of telomerase expression, and would have a greater benefit for HGPS ECs. HGPS ECs were treated with hTERT linear or circ RNAs. A single treatment with 1 µg/ml hTERT circRNA reversed multiple stigmata of senescence. However, at day 28 post treatment, the benefit of hTERT circRNA exceeded that of hTERT linear RNA in all measured variables. hTERT circRNA provided for greater recovery of telomere length as determined by quantitative fluorescence in situ hybridization; induced a three-fold greater reduction in beta-gal positive cells and morphologically aberrant nuclei. In HGPS ECs, hTERT circRNA provided for a 2-3 fold greater reduction of senescentfactors, inflammatory cytokines and DNA damage signals, including Progerin, p16, p21, IL-1B, IL-6, IL-8 MCP-1 and gH2A.X. In addition, hTERT circRNA to a greater degree restored NO production, promoted cell proliferation, enhanced angiogenesis and improved LDL uptake. Importantly, mitochondrial functions, as evaluated by the oxidative stress marker (MitoSOX) and mitochondrial membrane potential marker (JC-1 staining), were restored more completely by hTERT circRNA. Conclusion: hTERT circRNA is more effective than hTERT linear RNA in rejuvenating senescent ECs, possibly because of its longer half-life. The novel hTERT circRNA is a promising therapy for HGPS and other disorders associated with accelerated vascular aging.
Abstract 4146351: A Multicentre Study for Hands Only CPR (HOCPR) training assessment towards building a ‘Nation of Life Savers” in India
Authors: Thanjavur Ravikumar, Thanjavur Ravikumar, Manuj Sarkar, Dhrubajyoti Debnath, Priyamadhaba Behera, Dr Jayshri R Ghate, Divay Trikha, A Samantaray, K Madhavi, KVS Sarma
Journal: Circulation (2024)

Failure to rescue a subject sustaining sudden cardiac arrest is a public health issue requiring urgent action. The awareness, knowledge&amp;skills of HOCPR is very low and the need-gap is very high in India with world’s largest and diverse population (socioeconomic, cultural, linguistic&amp;educational). We undertook a structured multicentred approach with the following elements for improving HOCPR awareness, education&amp;training for generalisability and scalability: i) an IRB/IEC approved pre-post training survey; ii) train-the-trainer program iii) pilot study in one district of a state; iv) validation study in 5 states (data validation is available for 4 out of 5 sites as of now) located in disparate regions of India with part financial support through AHA grants in aid. The pilot cohort of 46,012 trainees covered 27 of 32 revenue divisions (mandals) in one state, comprising students and community members of diverse sections of society. Pre- post training statistical analyses include McNemer’s test&amp;ChiSquare. Results: The reason for non-readiness for HOCPR was” do not know how” in 92.9% of trainees in pre-test, and 98.6% reported that they learnt HOCPR in post -test(p&lt;0.001). Pre- post education/ training comparison statistical analysis showed a significant improvement in knowledge (p&lt;0.0001)&amp;skill (p&lt;0.0001). There was 82.8% improvement in knowledge, and 60.4% improvement in readiness; showing that ‘readiness’ requires more effort than knowledge/skills alone in HOCPR. The quality of training (Likert scale) showed 86% responding excellent/ very good; and the reasons for improvement being more training time and unevenness in quality of training in 14% of trainees. The ongoing validation study cohort comprises 59,646 trainees. Pre-post survey corroborated the pilot data with regards to knowledge/skills of trainees and quality of training. This prospective multicentre HOCPR training impact analysis provides scientific platform for scaling up in a most heterogeneous and vast population like India. Further studies are planned to improve HOCPR readiness as well as downstream analysis of sudden cardiac arrest victims receiving HOCPR at the scene for mitigation of death and enhanced quality of life of survivors transported to hospital.
Abstract 4146116: Carotid body ablation reduces hypertension following long-term intermittent hypoxia by regulating brainstem glial cell activation
Authors: Rodrigo Iturriaga, Katherine Pereyra, Sinay Vicencio, Ignacio Bernal, Esteban Diaz-Jara, Rodrigo Del Rio
Journal: Circulation (2024)

Introduction: Sleep apnea is an independent risk factor for hypertension. Chronic intermittent hypoxia (CIH), a key feature of sleep apnea, is considered the main factor for the development of hypertension, which is attributed to sympathoexcitation. However, novel evidence shows that CIH enhanced CB chemosensory discharges triggering an increase in sympathetic outflow through neuronal activation in the nucleus of the solitary tract (NTS). This idea is supported by the fact that CB ablation abolish the hypertension and NTS neuroinflammation after 21 days of CIH even in the presence of CIH. However, whether CB mediate glial cell activation (well-known sentinels involved in brain inflammation) following long-term CIH remains unknown. Hypothesis: Accordingly, we propose that the maintenance of hypertension and glia cell activation within the NTS of mice exposed to long-term CIH, depends on the CB afferent discharge. Methods: We exposed male C57BL6 mice to CIH (5% FiO2, 12 times/h, 8 h/day) for 60 days. At 45 days of CIH, CBs were selectively denervated, and animals were kept in CIH for additional 15 days. At the end of the experiments, we measured arterial blood pressure (MABP), hypoxic ventilatory response (HVR) in awake mice and assessed astrocyte and microglia activity through morphological 3D reconstructions, and IL-1β, IL-6, and TNF-α gene expression in the NTS with real-time PCR. Results: CIH induces hypertension (MABP 83.5±1.4 vs. 95.0±2.2 mmHg; Sham vs CIH), enhances HVR (1.69±0.2 vs 4.3±0.9 VE/min; Sham vs. CIH), and change astrocytes morphology (N° of branches 13.0±0.7 vs 11.3±0.5; cable length 181.0±8.9 vs 148.1±1.5 pm, Sham vs CIH), and microglia arborization (N° of branches 196.1±8.4 vs 376.3±16.8; cable length 667.4±29.6 vs 1267±60.5 pm, Sham vs CIH). Remarkably, CB denervation (CIHd) normalized the hypertension (MABP 83.5±1.4 mmHg; CIHd), the enhanced HVR (1.63±0.43 VE/min; CIHd), reduced the increased IL-6 (1.2± 0.2 vs 0.4 ± 0.1, CIH vs CIHd), TNF-α (2.0±0.2 vs 1.1±0.2, CIH vs CIHd) but not IL-1β levels (3.0±0.4 CIH vs 2.6±0.5, CIH vs CIHd), and the changes observed in astrocytes (N° of branches 17.2±0.9, cable length 231.0±12.9) and microglia (N° of branches 126.2±13.3; cable length 126.2±1.3 CIHd). Conclusions: Present results suggest that CBs plays a critical role in the maintenance of high blood pressure and contribute to the inflammation in the NTS of mice exposed to long-term CIH. Supported by Fondecyt Grants 1211443 and 1220950.
Abstract 4146445: The critical role of CD206+ pro-PAH macrophages in contributing to severe pulmonary arterial hypertension and obliterative vascular remodeling
Authors: Jingbo Dai
Journal: Circulation (2024)

Rationale: Previously we identified a mouse model Tie2Cre -mediated disruption of Egln1 of Pulmonary arterial hypertension (PAH) with progressive obliterative vascular remodeling including vascular occlusion and plexiform-like lesions and right heart failure. Tie2Cre-meidated disruption of Egln1 in bone marrow contributes to the severity of PAH indicating the importance of the immune cells in the pathogenesis of PAH. We hypothesized that Macrophage accumulation and polarization due to Egln1 deficiency contributes to obliterative pulmonary vascular remodeling and severe PAH in Egln1 Tie2Cre (CKO) mice. Methods: We utilized single-cell RNA sequencing (scRNAseq) to provide transcriptome insights into cellular composition changes in the lungs of in Egln1 Tie2Cre mice. Egln1 Tie2Cre mice with CD68-FlpERT2/CD206-frt-stop-frt-Dre/Rosa26-rox-stop-rox-DTR (CKO/Dep) transgene were generated and received tamoxifen and diphtheria toxin to deplete the CD206+ macrophages during the development of PAH. RVSP and RV/(LV+S) ratio were measured. Russell-Movat pentachrome staining was carried out to assess pulmonary vascular remodeling. Igf1 / Egln1 Tie2Cre double knockout mice and IGF1R inhibitor treatment were employed to delineate the molecular mechanism. Results: Single cell RNA sequencing and FACS analyses identified marked accumulation of the CD206+ macrophage subpopulation in Egln1 Tie2Cre mouse lungs. CD206 + Macrophages were accumulated in the pulmonary vessel adventitia of idiopathic PAH (IPAH) patients as well as Egln1 Tie2Cre mice. Genetic depletion of CD206+ macrophages using the Egln1 Tie2Cre /MaFIA mouse model markedly inhibited obliterative pulmonary vascular remodeling and PAH and promoted survival. These macrophages were PHD2-deficient and expressed elevated levels of pro-PAH factors such as IGF-1 and thus promoted SMC proliferation in co-culture study. Genetic disruption of the Igf1 in Egln1 Tie2Cre mice inhibited IGF-1 production and attenuated PAH and pulmonary vascular remodeling. Treatment of IGF1 receptor inhibitor attenuated PAH in Egln1 Tie2Cre mice and MCT-rats. Conclusions: PHD2 deficiency in hematopoietic cells induced accumulation of CD206+ macrophages in the adventitia of pulmonary vascular lesions of Egln1 Tie2Cre mice and IPAH patients, which contributed to severe PAH though the Igf1 signaling. Thus, targeting abnormal macrophage function and signaling pathways is a potential effective therapeutic strategy for treatment of PAH patients and promotion survival.
Abstract 4146263: Radiation Induced Valvular Heart Disease complicated by Concomitant Radiation Induced Coronary Artery Disease
Authors: Sean Basile, Ramesh Venkataraman, Robert Gallagher
Journal: Circulation (2024)

The cardiac adverse effects of radiation therapy include both radiation-induced valvular disease and radiation-induced coronary artery disease (RICAD). However, the management of each when present concurrently is minimally described by current research and guidelines. A 60 year-old infectious disease physician with history of Stage IIA Hodgkin Disease s/p radiation therapy in 1976 (age 13) presented to cardiology for new dyspnea on exertion. She had known valvular heart disease followed with serial echocardiograms. Repeat TTE completed showing now moderate to severe aortic stenosis, moderate aortic regurgitation, moderate tricuspid regurgitation, and mild to moderate mitral regurgitation. After exercise stress testing aborted due to decrease in systolic blood pressure with exertion, patient underwent cardiac catheterization and found to have moderate-severe aortic stenosis as well as hemodynamically significant ostial disease of the right coronary artery and distal left main coronary artery; classic bi-ostial coronary stenosis characteristic of RICAD. After multidisciplinary discussion with interventional cardiology, cardiothoracic surgery, and second opinion with tertiary valve center, she was referred for surgical revascularization and aortic valve replacement (AVR). Patient underwent AVR with a 23mm bioprosthetic aortic tissue valve replacement, aortic root enlargement, tricuspid valve repair with 28mm ring, and three vessel coronary artery bypass grafting. Notably, several retrospective studies have found increased mortality with surgical aortic valve replacement in patients with prior history of radiation with many centers preferring transcatheter aortic valve replacement as a safe and effective alternative in this demographic. Despite acknowledging this predilection, SAVR chosen in this patient specifically given her concurrent RICAD requiring revascularization. This case intimately highlights the need for further studies regarding management of radiation-induced valvular disease when complicated by RICAD.