tbuckley/cabot-search huggingface dataset:
Abstract 4148026: Multi-Venous Compression Syndromes Are Characterized by Preload Failure and Dysautonomia
Authors: Arvind Pandey, Magda Abdou, Marie Gerhard-Herman, Matthew Menard, David Systrom
Journal: Circulation (2024)

Introduction: Multi-venous compression syndromes pose diagnostic and management dilemmas due to uncertainties in both etiology and clinical course. Clinical thresholds for surgical intervention are unclear, and systemic symptoms beyond the anatomic sites of compression are common, including exertional dyspnea, intermittent tachycardia, and fatigue. We hypothesize that multi-venous compression syndromes may represent a manifestation of autonomic dysfunction with impaired venous return to the right heart (preload failure physiology). Methods: Consecutive patients presenting to the Vascular Medicine clinic, Vascular Surgery clinic, or the vascular ultrasound laboratory at Brigham and Women’s Hospital from November 1, 2021 to May 1, 2024 with evidence of multi-vein compressions were retrospectively included in this cohort. Venous compressions evaluated were thoracic outlet syndrome, popliteal entrapment, left common iliac vein compression, and left renal vein compression. Data were analyzed from autonomic function testing and invasive cardiopulmonary exercise testing (iCPET) performed for clinical indications. Results: A total of 16 patients presented with imaging-confirmed multi-vein compressions. The average (standard deviation) number of compressed sites were 4 (2). Eleven patients (69%) had clinical symptoms of dysautonomia. Five patients (31%) underwent autonomic function testing; all had an abnormal result, most commonly manifesting as reduced orthostatic cerebral blood flow velocity. Seven patients (44%) underwent iCPET; the average right atrial pressure at peak upright exercise was abnormally low at 1 mmHg (1.5 mmHg) with a range of 0-4 mmHg. Four out of 7 patients had accompanying peak oxygen consumption less than 80% of predicted. Seven patients (44%) underwent surgery for at least one compression; the most common procedure was left common iliac vein stenting. Two patients with dysautonomia underwent venous decompression and reported no significant change in overall symptoms. Nine patients with dysautonomia were managed conservatively with medical therapy (salt/water repletion, oral pyridostigmine, beta blocker, midodrine, and/or compression garments). Eight of these patients reported improved functional status after at least 6 months. Conclusions: Patients with multi-vein compressions are enriched for autonomic dysfunction and preload failure. Medical therapy can improve overall functional status without requiring surgical intervention.
Abstract 4147915: Title: Cardiovascular Events Associated with Endothelin Receptor Antagonists: A Pharmacovigilance Analysis of Bosentan and Ambrisentan
Authors: Azeem Rathore, Sadhana Jonna, Daniel Hanna, Dhiran Verghese, Laura Muller, Juan Sierra, Elsy Navas, Mehdi Mirsaeidi
Journal: Circulation (2024)

Introduction: Endothelin receptor antagonists (ERAs) are the mainstay therapy for pulmonary arterial hypertension (PAH). However, there is limited data on cardiac adverse drug events (ADEs) associated with ERA medications. We performed a pharmacovigilance study comparing bosentan and ambrisentan using the FDA Adverse Event Reporting System (FAERS) data. Methods: Cardiac ADE data for bosentan and ambrisentan from January 1, 2004, to December 31, 2023, in the FAERS database were retrieved. Disproportionality analysis was performed by calculating the reporting odds ratio (ROR) aligned with p-values. The following cardiac ADEs were included: atrial fibrillation (AF), right ventricular failure (RVF), and cardiac arrest (CA). Results: For adults ≥ 18 years, a total of 12,058 cardiac ADEs were reported for both bosentan (38%) and ambrisentan (62%). Among the selected cardiac ADEs, AF was more frequently reported with bosentan (ROR 3.99, 95% CI: 3.62-4.40) than ambrisentan (ROR 1.91, 95% CI: 1.77-2.07). RVF showed a significantly higher ROR for bosentan (73.60, 95% CI: 66.68-81.25) than ambrisentan (23.11, 95% CI: 20.99-25.46). CA was also more commonly associated with bosentan (ROR 2.25, 95% CI: 1.98-2.55) than with ambrisentan (ROR 0.69, 95% CI: 0.61-0.78), with all comparisons showing p-values &lt; 0.001. Conclusion: Our study identifies a significantly higher frequency of cardiac ADEs, particularly AF, RVF, and CA, in patients treated with bosentan compared to ambrisentan. This finding corroborates previous literature that has suggested differential safety profiles among ERAs, emphasizing the need for vigilant cardiac monitoring. Clinicians should integrate these insights into their practice, potentially favoring ambrisentan in patients with elevated cardiac risk, thus optimizing the management of PAH and improving patient outcomes.
Abstract 4147874: Plasmalemma Vesicle-Associated Protein (PLVAP) regulates Cardiac Endothelial Permeability is ARNT-dependent
Authors: Md Karim Ullah, Qiong Wu, zainab humayun, Jing Jiang, Snekha Rajasekaran, Ha Ram Kim, Yun Fang, Rongxue Rosie Wu
Journal: Circulation (2024)

Background: Disruption of microvascular endothelial integrity significantly contributes to ischemic cardiovascular injury. PLVAP is an endothelial-specific integral membrane glycoprotein localized to caveolae and fenestrae, predominantly expressed in cardiac microvascular endothelial cells (CMVECs). The precise role of PLVAP and its regulatory mechanisms remain unclear. We hypothesize that Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) modulates PLVAP to regulate cardiac barrier function. Methods and Results: We utilized primary CMVECs isolated from inducible endothelial-specific ARNT knockout (KO) mouse hearts and human CMVECs treated with siRNA. ARNT deletion resulted in reduced PLVAP expression at both protein and mRNA levels (P &lt; 0.0001). Chromatin immunoprecipitation followed by qPCR (ChIP-qPCR) confirmed that ARNT binds to the PLVAP promoter region, indicating transcriptional regulation of PLVAP by ARNT. Promoter assays further demonstrated that ARNT regulates PLVAP expression (P &lt; 0.0001). Immunofluorescence staining with wheat germ agglutinin (WGA) revealed a significant reduction in the glycocalyx layer in PLVAP-deleted human microvascular endothelial cells, alongside decreased expression of endothelial junctional proteins VE-Cadherin and Occludin. Conversely, activating ARNT/HIF1α heterodimers using a prolyl-4 hydroxylase inhibitor (DMOG) or overexpressing ARNT restored the endothelial glycocalyx, permeability, and VE-Cadherin expression in LPS-stimulated cells. Furthermore, ARNT activation increased the size of plasmalemma vesicle pores and heightened endothelial permeability in human primary endothelial cells. Conclusions: This study highlights the vital role of the endothelial ARNT in regulating PLVAP which controls vascular permeability. These findings provide insights into the molecular mechanisms of endothelial permeability and identify potential therapeutic targets for treating vascular and cardiac complications.
Abstract Sa807: Spread of Chest Compression-Only CPR During the COVID-19 Pandemic Increased Pediatric Out-of-Hospital Cardiac Arrest Mortality: A Nationwide, Retrospective, Observational Study
Authors: Takafumi Obara, Hiromichi Naito, Naomi Matsumoto, Kohei Tsukahara, Tsuyoshi Nojima, Takashi Hongo, Tetsuya Yumoto, Takashi Yorifuji, Atsunori Nakao
Journal: Circulation (2024)

Background: Despite the lack of evidence supporting the use of chest compression-only cardiopulmonary resuscitation (CO-CPR) emphasizing the importance of rescue breathing for pediatric out-of-hospital cardiac arrest (OHCA), prehospital CO-CPR is increasing. The COVID-19 pandemic may have led more bystanders to perform CO-CPR, even for pediatric OHCA. However, studies on the dissemination of CO-CPR and outcomes in pediatric OHCA are limited. Hypothesis: Spread of CO-CPR led to increased mortality in pediatric OHCA. Aims: Investigate the mortality of nationwide pediatric OHCA patients with the dissemination of CO-CPR pre- and post-COVID-19. Methods: We conducted a retrospective study using a Utstein-Style population cohort database (Japanese National Registry). Pediatric OHCA patients (≤17 years old) with bystander resuscitation attempts registered between the pre-COVID-19 era (2017-2019) and the post-COVID-19 era (2020-2021) were included. The primary outcome was 30-day mortality after OHCA. The secondary outcome was 30-day poor neurological outcomes, defined as Cerebral Performance Category scores of 3, 4, or 5. We used Poisson regression with robust variance to estimate adjusted risk ratio (aRR) with 95% confidence interval (CI) and the population attributable fraction (PAF, %) with a focus on the post-COVID-19 period. Results: A total of 3,352 pediatric OHCA, 2,023 pre-COVID-19, and 1,329 post-COVID-19 patients received bystander CPR and were registered in the database. CO-CPR was more common than CPR with rescue breathing (RB-CPR) during the pre- and post-COVID-19 periods [pre-COVID-19: 1,356 (67.0%) vs. 667 (33.0%), post-COVID-19: 1,048 (78.9%) vs. 281 (21.1%)]. Comparison of CO-CPR vs. RB-CPR showed increased 30-day mortality in both periods [pre-COVID-19: 1,081/1,356 (79.7%) vs. 420/667 (63.0%), post-COVID-19: 841/1,048 (80.2%) vs. 181/281 (64.4%)]. In the overall cohort, mortality increased with CO-CPR (aRR: 1.16, 95% CI: 1.09-1.23, PAF:1.60%). Due to the increased number of patients receiving CO-CPR, we estimated 21.2 excess deaths over the two-year post-COVID-19 period. Similar results were observed for poor neurological outcome (aRR: 1.10, 95% CI: 1.05-1.16, PAF: 1.10%, excess poor outcome: 14.6]). Conclusion: With the spread of CO-CPR for pediatric OHCA, an estimated 10.6 excess deaths per year attributed to CO-CPR may have occurred in the post-COVID-19 period compared to the pre-COVID-19 period in Japan.
Abstract Sa401: Bystander Cardiopulmonary Resuscitation in Out-of-Hospital Cardiac Arrest Cases in Chicago
Authors: Shaveta Khosla, Marina Del Rios, Pavitra Kotini-Shah, Courtney Schwerin O'Reilly, Elizabeth Froelich, Brenice Fokum, Teri Campbell, Eddie Markul, Katie Tataris, Joseph Weber, Terry Vanden Hoek
Journal: Circulation (2024)

Introduction: Bystander cardiopulmonary resuscitation (CPR) improves survival in out-of-hospital cardiac arrest (OHCA) cases. Nationally and locally, consistent efforts have been made in increasing awareness and training the public in CPR. In this study, we assessed the changes in bystander CPR rates over time, overall and by sex and race/ethnicity in Chicago. Methods: We analyzed OHCA cases served by Chicago Emergency Medical Services from 2014-2023. We excluded trauma cases, pediatric cases, cases that were missing bystander CPR information, cases from nursing homes and healthcare facilities, and cases from international airports. Average annual change was assessed along with a p-value for trend. Results: Of the 21,862 OHCA cases reported from 2014-2023, 58% were Black, 14% Hispanic and 24% White, and the remaining were categorized as other. Overall, the bystander CPR rate increased from 12.4% in 2014 to 43.9% in 2023. Yearly rates of bystander CPR improvement were initially inconsistent, but the rates have risen consistently since 2018 (with an average annual change of +5%, p=0.003). Similar trends have been seen by race/ethnicity and sex. In White cases, the bystander CPR increased from 19% to 47% from 2014 to 2023 (average annual change of +6.2% from 2020 onwards, p=0.047). In Hispanic cases, the bystander CPR increased from 17% to 51% from 2014 to 2023; however, the increase was not consistent from year to year. During the same time period, bystander CPR increased in Black cases from 8% to 41% (average annual change of +5.4% from 2018 onwards, p=0.001). From 2014 to 2023, bystander CPR increased from 15% to 44% (annual change of +4.8% from 2018 onwards, p=0.005) in males, and from 9% to 43% (annual change of +5.4% from 2018 onwards, p=0.004) in females. Conclusion: Bystander CPR rates have improved significantly in Chicago. Since 2020, sharp increase in bystander CPR rates is coinciding with overall improvement in OHCA survival in Chicago. The impact of bystander CPR on survival in different racial/ethnic groups requires further study.
Abstract 4148133: Association between small pre-implant left ventricular end diastolic diameter and post left ventricular assist device implantation all-cause mortality: A systematic review and meta-analysis
Authors: Adhvithi Pingili, Mounika Reddy Vadiyala, Kumar Anmol, Muskan Jain, Jeffy Susan Varghese, Vibhor Ahluwalia, Kesar Prajapati, Vardhan Chalasani, Rupak Desai, Erika Feller
Journal: Circulation (2024)

Background: Left ventricular assist devices (LVADs) are crucial for the management of advanced heart failure patients acting, both as a bridge to heart transplant or destination therapy. Existing studies revealed mixed results on the impact of pre-implant left ventricular end-diastolic diameter (LVEDD) on post-LVAD mortality. Some studies found smaller LVEDD increases mortality, while others revealed no significant impact. Due to the limited evidence, this meta-analysis aims to determine the association between pre-LVEDD and post-LVAD implantation mortality through a systematic review and meta-analysis. Method: We systematically reviewed articles until May 2024 examining the association between pre-implant LVEDD and post-LVAD implantation mortality using PubMed, Google Scholar, Embase, and Scopus. A random effects model was used to calculate the pooled adjusted odds ratio (aOR). We used I 2 statistics to determine the heterogeneity of studies. Leave-one-out sensitivity analysis was done to evaluate each study's effect on the overall estimate, with statistical significance set at p&lt;0.05. Results: We included four studies in our meta-analysis, three from the USA and one multicountry study, totaling 16,548 LVAD recipients (13,110 males and 3,438 females). We examined the relationship between pre-implant left ventricular end-diastolic diameter (LVEDD) and mortality following continuous LVAD implantation. The random-effects model revealed a significant association between smaller LVEDD and increased mortality, with a pooled adjusted odds ratio (aOR) of 1.29 [95% confidence interval (CI): 1.10 – 1.53, p &lt; 0.01]. Leave-one-out sensitivity analysis validated the robustness of our findings, identifying the study by Dual et al. as the most influential. We observed low heterogeneity among the included studies (I 2 =22.38 %, P=0.28), suggesting consistent results across different populations and settings. Conclusion: Our study demonstrates a significant association between small pre-implant LVEDD and higher post-LVAD implantation mortality when compared to large pre-implant LVEDD. Overall, our results underscore the need for careful assessment of LVEDD in clinical decision-making and patient management for those undergoing LVAD implantation.
Abstract Sa403: Chest Compression Metrics During Adult In-Hospital Cardiopulmonary Resuscitation: A GWTG-Resuscitation Study
Authors: Amanda O'Halloran, Ryan Morgan, Jessica Alvey, Ron Reeder, Elizabeth Patterson, Tia Raymond, Sarah Perman, Dana Edelson, Heather Wolfe, Vinay Nadkarni, Robert Berg, Benjamin Abella, Robert Sutton
Journal: Circulation (2024)

Background: CPR quality is an important modifiable component of cardiac arrest care. Current chest compression (CC) guidelines were primarily generated from out-of-hospital arrest data. However, they are applied to cardiac arrests in all contexts, including in-hospital. Aims: We aimed to: 1) quantitatively describe in-hospital cardiac arrest (IHCA) CC metrics; 2) determine the association of current AHA guideline-recommended CC metrics with IHCA outcomes; and 3) discover new CC targets using IHCA data and quantify their association with outcomes. We hypothesized that existing CC targets (rate 100-120 compressions per minute [cpm], depth 50-60 mm, CCF&gt;80%) would be associated with improved outcomes. Methods: Retrospective cohort using the AHA GWTG-Resuscitation adult IHCA registry. Events in 2015-2022 lasting ≥1 min with recorded CC metrics were included. To discover alternative CC targets, we utilized a combination of cubic splines, ROC curves, and clinician judgment. Multivariable logistic regression evaluated the association between exposures (guideline-recommended depth [50-60 mm], rate [100-120 cpm], CCF [&gt;80%]; novel targets for depth, rate, CCF) and outcomes (primary: survival to discharge; secondary: survival with favorable neurological outcome). Results: Of 587,588 IHCAs, 3391 events at 42 sites were included (rate: n=3380; depth: n=2892; CCF: n=2698). Median age was 65 years [IQR 54, 73]. Median rate was 112 cpm (IQR 105, 120); depth 61 mm (IQR 53.3, 68.6); and CCF 90% (IQR 82%, 95%). There was no association between current guideline-recommended CC targets and survival to discharge (rate: aOR 1.08 [95CI 0.88, 1.32], p=0.46; depth: aOR 0.88 [95CI 0.71, 1.08], p=0.22; CCF: aOR 0.79 [95CI 0.62, 1.01], p=0.058). In our spline/ROC curve analysis, we identified alternative targets of rate 100-110 cpm, depth 40-50 mm, and CCF&gt;95%, which were associated with higher odds of survival to discharge (rate: aOR 1.32 [95CI 1.10, 1.58], p&lt;0.01; depth: aOR 1.41 [95CI 1.07, 1.86], p=0.015; CCF: aOR 2.08 [95CI 1.67, 2.60], p&lt;0.01) and survival with favorable neurological outcome (rate: aOR 1.38 [95CI 1.13, 1.69], p&lt;0.01; depth: aOR 1.52 [95CI 1.14, 2.05], p&lt;0.01; CCF: aOR 2.14 [95CI 1.66, 2.75], p&lt;0.01). Conclusions: In this adult IHCA study, contrary to our hypothesis, existing guideline-recommended CC targets were not associated with outcomes. Alternative targets derived from GWTG-R (rate 100-110 cpm; depth 40-50 mm; CCF&gt;95%) were associated with improved outcomes.
Abstract Sa406: Stayin’ Alive: Establishing a Rhythm With Resuscitation Data
Authors: Christine Quindipan, Michelle Antiporda, Natalie de Haas, Beanet Solorzano, Peter Marshall, Bessie Rivera
Journal: Circulation (2024)

An interprofessional care model was implemented in 2020 to improve CPR care outcomes based on AHA’s Get With the Guidelines (GWTG) – Resuscitation program. The program provided measures ensuring high-quality care was delivered during cardiopulmonary arrests (CPA). Compliance required &gt;85% for all four measures, which included: confirmation of airway, time to first shock ≤2 minutes for VF/pulseless VT, time to IV/IO epinephrine ≤5 minutes for asystole/PEA, and percent of pulseless cardiac events monitored. Keck Hospital of USC had lost its GWTG award status several years prior to the establishment of the interprofessional team, which consisted of a Physician Champion, CNS, RN Quality Specialist, LVN Quality Data Abstractors and the director of HIM. The primary goals of the team were to improve the workflow of data collection, standardize documentation, and ultimately increase compliance of the measures. The Lean Six Sigma methodology was applied revealing gaps in data collection. HIM and Quality collaborated in developing a systematic method to improve electronic data availability. To decrease documentation variations, the CNS revised CPA forms and the Physician Champion created a standardized electronic Code Blue summary template. Once collected, data was systematically analyzed by the Quality team members to ensure data accuracy and to highlight areas of opportunities for improvement. Findings were then presented on a quarterly basis during the Critical Care and Resuscitation committees chaired by the CNS and Physician Champion. Additionally, the CNS implemented evidence-based practices which included assigning code roles to ICU personnel, educating ICU staff, performing monthly mock codes, and completing weekly reviews of CPA forms that included communicating documentation discrepancies to clinicians. Since the implementation of the team, sustained efforts have succeeded in improving resuscitation care outcomes. Substantial progression was evident in the time to first shock and confirmation of airway measures. In 2020, the hospital had a 69.2% compliancy rate for time to first shock. By 2022, we were performing at 89.5%. For confirmation of airway, we began at 72.4% in 2020; and within one year was at a 95.5% compliancy rate. This achievement continued into 2022 with a rate of 94.9%. Lastly, we achieved &gt;85% compliancy for all four measures receiving AHA’s Gold Award for outstanding performance for two consecutive years (2022&amp;2023).
Abstract 4147898: Bromodomain-containing protein 4 Mediates TGF-β-induced Smooth Muscle Cell Differentiation
Authors: Xia Guo, Ayobami Olajuyin, Venkatakirankumar Mandlem, Christudas Sunil, Yunzhuan Hou, Oluwaseun Adeyanju, Sana Petkar, Guoqing Qian
Journal: Circulation (2024)

Vascular smooth muscle cell (VSMC) differentiation is an essential component of vascular development. VSMCs are not terminally differentiated cells. They switch their phenotypes between proliferative and differentiated states, which is a major factor contributing to vascular diseases like atherosclerosis, aneurysms, hypertension, etc. Transforming growth factor-β (TGF-β) plays an essential role in VSMC differentiation. However, the detailed mechanisms remain incompletely understood. Bromodomain-containing protein 4 (BRD4) belongs to the family of bromodomain and extra-terminal domain (BET) proteins. It is an epigenetic modulator that has been implicated in different human diseases including cancer and tissue fibrosis. However, whether BRD4 mediates TGF-β-induced SMC differentiation remains unclear and was explored in this study. We found that TGF-β induced 10T1/2 cells (a mesenchymal stem cell line) to express markers of SMCs in a time dependent manner. Interestingly, the BRD4 inhibitor JQ1 and degrader ARV-825 effectively blocked the differentiation of 10T1/2 cells towards SMCs induced by TGF-β, as indicated by decreased induction of SMC markers such as SM22α and α-SMA. Knockdown of BRD4 using siRNA also significantly decreased TGF-β-induced differentiation of 10T1/2 cells towards SMCs. TAZ is a mediator of TGF-β-induced SMC maker gene expression. BRD4 inhibition attenuated TGF-β-induced TAZ expression, suggesting that BRD4 may regulate SMC differentiation through TAZ expression. In addition, BRD4 mediates the binding between TAZ and Smad3 to regulate the SMC marker gene transcription. Take together, our findings suggest that BRD4 modulates TGF-β-induced SMC differentiation and might play a role in SMC differentiation-related vascular diseases.