tbuckley/cabot-search huggingface dataset:
Abstract 4116141: Von Willebrand Factor Inhibition by BB-031 Prevents and Thrombolyses Clots in a Murine Model of Venous Thrombosis
Authors: Arianna Carfora, Dominic Franceschelli, Mayur Patel, Debra Wheeler, Roman Covarrubias, Oscar Bermeo-Blanco, Richard Gumina, Shahid Nimjee
Journal: Circulation (2024)

Introduction: Venous thromboembolism (VTE) manifesting as deep vein thrombosis and pulmonary embolus results in ~300,000 US deaths annually. Risk factors include obesity and current therapy limitations leave ~ 50% of patients with no effective treatment. Circulating von Willebrand Factor (VWF) levels portend poor clinical outcomes. BB-031, an aptamer-based VWF inhibitor with prophylactic and arterial thrombolytic efficacy may translate to VTE. Methods: Jugular vein occlusion (JVO) was induced by FeCl 3 either before or after intravenous treatment in 14 week old male and female C57/BL6 wild type (WT) or male diet-induced obese (DIO) mice. 5.0 mg/kg BB-031 was administered as a bolus, 10.0 mg/kg rtPA with 10% bolus and remaining 90% over 60 minutes, 400 U heparin as a bolus, or vehicle. Doppler jugular vein flow velocity was recorded from baseline to determine patency 30 minutes after injury. Thrombolytic clots were stabilized for 20 minutes. Results: Prophylactic mice occluded ~20 minutes after FeCl 3 application with rtPA=18.32 +/- 6.54 min, heparin 17.14 +/- 8.53 min, and vehicle 17.29 +/- 7.26 min. Thrombosis did not occur with BB-031 treatment (n=4-12/group). Treatment after JVO resulted in no difference compared to vehicle in male WT mice, but BB-031-treated WT females resulted in 76.09% recanalization 35 minutes after occlusion compared to rtPA (9.64%, p&lt;0.0001), heparin (30.95%, p=0.7306), or vehicle (22.07%, p&lt;0.0001), (n=5/group). Male DIO mice significantly reperfused with BB-031 (100%) vs rtPA (10.52%), heparin (4.54%), and vehicle (22.50%), p&lt;0.0001, (n=4-6/group). Conclusion: VWF inhibition by BB-031 maintains patency in a VTE murine model offering future therapeutic alternatives.
Abstract 4113864: Hyperkalemia In Patients With Heart Failure Correlates to Worse Inpatient Outcomes
Authors: Mohamad Alhoda Mohamad Alahmad
Journal: Circulation (2024)

Background: Heart failure (HF) is one of the leading causes of hospitalizations in the States. Hyperkalemia is not an infrequent comorbidity in patients with HF, limiting the maximum benefits of guideline-directed medical therapy. This study evaluates the outcomes in patients admitted for HF with and without hyperkalemia. Methods: We used the Nationwide Readmissions Database (NRD) from 2016-2019, extracting adult patients with a primary diagnosis of HF who were admitted between January and November of each year. Survey procedures were applied using SAS 9.4. Results: We included 4,454,273 weighted hospitalizations due to HF for which 380,446 patients (8.5%) had a concurrent diagnosis of hyperkalemia. Overall, patients with hyperkalemia, compared to HF cases with hyperkalemia, were slightly younger (mean age 70 years vs. 72 years, p &lt;0.01) with fewer women (47% vs.48%) respectively. Patients with hyperkalemia had a higher frequency of diabetes mellitus, hypertension, chronic liver disease, acute kidney injury, chronic kidney disease, end-stage renal disease, and acute encephalopathy (p&lt;0.001). They had more inpatient complications including ventricular fibrillation and cardiac arrest (p &lt;0.001) with longer mean lengths of stay (7 days vs. 5 days, p &lt;0.001) and 30-day readmissions (28% vs. 22%, p&lt;0.001). In-hospital mortality during index admission was significantly higher in the hyperkalemic group (6.4% vs. 2.5%, p &lt; 0.001). Inpatient outcomes including mortality were also worse during first readmission (7% vs. 6%, p&lt;0.01). Even after adjustment for the above-mentioned comorbidities, multivariable analysis reveals that hyperkalemia is an independent factor for inpatient mortality (adjusted OR 1.9 [1.8-2], p&lt;0.001). Conclusion: Hyperkalemia in patients admitted with HF is associated with increased inpatient mortality and readmission. Further studies can investigate whether novel potassium binders may improve outcomes.
Abstract 4113494: Gut Microbiota Modulation by Immunosuppression and Cardiac Cell Therapy in a Nonhuman Primate Ischemia/Reperfusion Model of Cardiac Regeneration
Authors: Patrick Hsieh
Journal: Circulation (2024)

End-stage ischemic heart disease necessitates heart transplantation, and emerging cell therapy presents a promising solution to address donor scarcity. Disruption of gut microbiota significantly influences various diseases and treatments, including transplantation. However, the impact of immunosuppression and cardiac cell therapy on gut microbiota remains largely unexplored. To elucidate this relationship, we investigated gut microbiota dynamics in response to immunosuppression and cell therapy in a nonhuman primate (NHP) cardiac ischemia/reperfusion (IR) model, with controlled genetic, dietary, and environmental factors. Immunosuppression enriched anaerobes (Faecalibacterium, Streptococcus, Anaerovibrio, Dialister), increasing gut microbiota diversity. These changes correlated with metabolic shifts towards amino acid metabolism and nucleosides/nucleotides biosynthesis. Combined treatment of human induced pluripotent stem cell (iPSC)-derived endothelial cells (EC) and cardiomyocytes (CM) also increased gut microbiota diversity, with specific genera alterations. The EC/CM co-treatment group displayed gut microbiota resembling the pre-injury group, with host metabolism shifting towards amino acid and fatty acid/lipid biosynthesis post-cell therapy. These observed microbiota changes and metabolic shifts could serve as biomarkers for monitoring cell therapy and immunosuppression outcomes, offering potential therapeutic targets to enhance efficacy.
Abstract 4117397: SGLT2i And Cardio-Renal Outcomes In Type 2 Diabetes Mellitus: A Systematic Review And Meta Analysis.
Authors: Carlos Zavaleta Corvera, Carlos D Surco-Larico, Betty Rivas-Leiva, MARINA ATENA BUSTAMANTE ORDOÑEZ, Eduardo Marchand Bayona, Jose Caballero-Alvarado
Journal: Circulation (2024)

Background: Diabetes Mellitus (DM) significantly impacts global health through cardiovascular and renal complications. SGLT2 inhibitors (SGLT2i) have emerged as beneficial for cardiovascular outcomes in Type 2 Diabetes Mellitus (T2DM). However, only few studies report outcomes related to renal function. Aim: This study aims to analyse the efficacy of SGLT2i on cardiorenal outcomes in adults with T2DM. Methods: A systematic review and meta-analysis, following PRISMA-2020 guidelines was conducted. We evaluated the efficacy of SGLT2i on cardiorenal outcomes in adults with T2DM. We included randomized controlled trials(RCT) and post hoc analyses that compared SGLT2i with placebo, focusing on cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalizations, and renal outcomes such as the progression of albuminuria and the decline of eGFR. Dichotomous outcomes were calculated using relative risk (RR) with 95% confidence interval (CI). Results: We identified 2753 studies, registered in PubMed(=788), Embase(n=538), WoS(n=369), Scopus(n=908), and Cochrane(n=150). We included 11 studies 6 RCT and 7 Post Hoc Analysis, sample size of 50.653 patients. Meta-analysis showed that SGLT2i improve cardiovascular outcomes such as reduced cardiovascular mortality (RR 0.84 [95% CI 0.73–0.97] p=0.02), heart failure hospitalizations (RR 0.65 [95%CI 0.54–0.77]p&lt;0.00001), and their composites outcomes. Furthermore, renal outcomes with SGLT2i significantly improve Urinary Albumin-to-Creatinine Ratio (RR1.10 [95%CI 1.03–1.18]p=0.004), Improvement of the decline of the eGFR (RR1.08 [95%CI 1.04–1.11] p&lt;0.00001) and progression of albuminuria (RR 0.69[95%CI 0.66–0.72]p&lt;0.00001). Slower Doubling of serum creatinine (RR 0.71 [95% CI 0.61–0.82] p&lt;0.00001), end-stage kidney disease (RR 0.66 [95% CI 0.53–0.83] p=0.0003). Reduced Acute Kidney Injury (RR 0.72 [95% CI 0.58–0.89] p=0.002) and renal impairment (RR 0.57 [95% CI 0.34–0.95] p=0.03). Regarding death from renal causes, we identified a 46% relative reduction in the risk in SGLT2i group, although was not statistically significant (RR 0.54 [95% CI: 0.23, 1.27] p=0.16). The observed heterogeneity across studies calls for careful application of these results to individual patients. Conclusion: SGLT2i confers notable advantages in managing cardiorenal complications in T2DM, demonstrating a reduction in cardiovascular mortality and heart failure hospitalizations and offering a nephroprotective effect.
Abstract 4124120: Rare but Deadly - Eosinophilic Myocarditis in a Patient with Eosinophilic Granulomatosis Polyangiitis
Authors: Samantha Shetty, Priya Shah, Yee Soo Kim, Angel De La Cruz Tejada, Ankitha Radakrishnan, Anya Srikureja, Adam Jacobi, Mary Beasley, Kiran Mahmood
Journal: Circulation (2024)

Eosinophilic myocarditis (EM) is a rare inflammatory myocarditis characterized by eosinophilic infiltration of myocardial tissue. Despite the high mortality rate, EM is frequently underdiagnosed and is often first identified in postmortem studies. We share a case of EM as an early manifestation of newly diagnosed eosinophilic granulomatosis polyangiitis (EGPA). The patient is a 46-year-old female with a past medical history of ulcerative colitis and adult-onset asthma who presented to the emergency department with a 2–3-week history of worsening positional chest pain radiating to the left upper extremity. Associated symptoms include 3 months of fatigue, headaches, right foot neuropathy, urticaria, and B-symptoms. Prior to admission, the patient was started on empiric prednisone for presumed EGPA. Initial lab work on admission was notable for elevated troponin (602 ng/L), hyper-eosinophilia (19.5%), thrombocytosis (680K/uL), and elevated ESR (42 mm/h) that have improved since initiation of prednisone. Transthoracic echocardiogram revealed a newly reduced LVEF of 40% with basal and mid-septal wall motion abnormalities. Cardiac catheterization showed normal coronaries confirming the diagnosis of non-ischemic cardiomyopathy. Late gadolinium enhancement in cardiac MRI was seen in basal to mid segments with patchy pericardial enhancement, meeting the Lake Louise criteria for myocarditis. An endomyocardial biopsy showed substantial myocardial infiltration with lymphocytes, histiocytes and eosinophils, confirming the diagnosis of EM. After multidisciplinary team discussion with cardiology and rheumatology, the patient was started on guideline-directed medical therapy for her HFrEF and pulse dose steroids with a prolonged taper and cyclophosphamide. She is tolerating her treatment well. This case highlights the importance of early recognition, comprehensive assessment and targeted treatment for EM depending on its underlying etiology. In the case of autoimmune dysfunction, it involves a combination of immunosuppressive and symptomatic therapy. Ongoing research is crucial to enhance our understanding and improve clinical outcomes, like arrhythmias and cardiogenic shock, for this complex condition.
Abstract 4116844: Simplifying Cardiology Research Abstracts: Assessing ChatGPT's Readability and Comprehensibility for Non-Medical Audiences
Authors: Kabir Malkani, Ruina Zhang, Zachary Falk, Prianca Tawde, Ryan Hughes, Melissa Parker, Griffin Collins, Danielle Maizes, Alexander Zhao, Vinay Kini
Journal: Circulation (2024)

Background: Artificial Intelligence (AI)-powered chatbots like ChatGPT are increasingly used in academic medical settings to help with tasks such as evidence synthesis and manuscript drafting. They have shown potential in simplifying complex medical texts for non-medical audiences like patients and journalists. However, less is known about whether simplified texts may exclude important information or be of interest to patients or other non-medically-trained people such as journalists. Objective: This study aims to assess ChatGPT's capacity to simplify cardiology research abstracts by eliminating jargon and enhancing universal comprehension. Methods: We analyzed all abstracts and scientific statements published from July to November 2023 in Circulation (n=113). These abstracts were processed through ChatGPT with the prompt: "Please rewrite the following text to be comprehensible at a 5th-grade reading level. Retain all original information and exclude nothing". We assessed the readability of both original and simplified texts using Flesch-Kincaid Grade Level (FKGL) and Reading Ease (FKRE) scores. Additionally, a panel of five physicians and five laypeople evaluated these texts for completeness, accuracy, and understandability. Results: ChatGPT transformation or abstracts reduced the required reading level from a college graduate to 8-9th grade by both FKGL (18.3 to 8.6; p&lt;.001) and FKRE (14.6 to 68.5; p&lt;.001). The physician panel generally found that the simplified abstracts retained all essential information without introducing errors. Both physicians and laypeople found the simplified texts more comprehensible. Laypeople appreciated the ease of understanding but did not strongly express a desire for more such simplified texts, and some still worried about the simplified abstracts missing important details. Conclusion: ChatGPT simplifies medical research abstracts to a level understandable by those with less than a high school education without excluding important information. This approach may be useful to communicate new research findings to patients and other non-medically-trained people.
Abstract 4118242: Impact of Pregnancy on Individuals with Hypertrophic Cardiomyopathy: Long-Term Clinical Outcomes - Population-Based Study
Authors: Omar Abdelfattah, Jasmin Abdeldayem, Danielle El Haddad, Garima Sharma, AMY AHNERT, Matthew Martinez, Baha Sibai, Wissam Khalife
Journal: Circulation (2024)

Background: The effect of pregnancy on individuals with Hypertrophic Cardiomyopathy (HCM) is not well investigated. Objective: To assess the impact of pregnancy on all-cause mortality and clinical outcomes among individuals with HCM Methods: Using the TriNetX research network, we identified individuals within reproductive age ( ≥ 18-45 years) with a diagnosis of HCM between 2012 and 2022 (n=10,936). Patients were stratified based on pregnancy history into two groups (a) those with a history of pregnancy/high-risk pregnancy supervision and (b) those without a history of pregnancy or subsequent antenatal/pregnancy supervision encounters throughout the study period. Propensity-score matching resulted in 3,399 patients in each cohort. The primary outcome was all-cause mortality. Secondary outcomes include a composite of arrhythmic events (SCD and SCD equivalents), major adverse cardiovascular events (MACE), and acute heart failure (HF) exacerbation during 10 years of follow-up. Results: Pregnancy in patients with HCM was associated with a comparable risk of all-cause mortality (adjusted OR:0.89; 95% CI: 0.7-1.14; p =0.37) at 10 years follow-up. MACE and acute HF exacerbation outcomes were lower in the pregnancy group; however, the arrhythmic events (SCD) did not differ between groups (adjusted OR: 0.93, 95%CI: 0.73-1.18; p =0.55). Conclusion: Pregnancy in individuals with HCM was not associated with a higher risk of adverse outcomes at long-term follow-up. Further efforts are warranted to better understand the short-term outcomes in this high-risk population
Abstract 4113617: Single-cell Analysis Reveals Endothelial Cell CD45 Deficiency Prevents Endothelial-to-Mesenchymal Transition (EndMT) in Atherosclerosis
Authors: Qianman Peng, Kulandai Samy Arulsamy, Yao Wei Lu, Bo Zhu, Kathryn Li, Bandana Singh, Hao Wu, Kui Cui, SHAHRAM EISA-BEYGI, Sana Nasim, Jill Wylie-Sears, Marina Malovichko, Liang Sun, Scot Wong, Douglas Cowan, Sanjay Srivastava, Da-Zhi Wang, Kaifu Chen, Joyce Bischoff, Hong Chen
Journal: Circulation (2024)

Introduction: Protein-tyrosine-phosphatase CD45 is exclusively expressed in all nucleated cells of the hematopoietic system but is rarely expressed in endothelial cells (ECs). However, a recent study indicated that activation of the endogenous CD45 promoter in human endothelial colony forming cells induced expression of EndMT marker genes. Also, the CD45 phosphatase inhibitor blocked EndMT activities in TGFβ1-treated ovine mitral valve endothelial cells. EndMT contributes to atherosclerotic pathobiology and is associated with more complex plaques. We identified CD45-positive ECs undergoing EndMT in atherosclerotic ApoE-deficient (ApoE -/- ) mice. Here, we aim to investigate whether endothelial CD45-specific deletion can prevent EndMT in a mouse model of atherosclerosis. Methods and Results: We generated a tamoxifen-inducible EC-specific CD45-deficient mouse strain (EC-iCD45KO) on an ApoE -/- background (C57BL/6) and fed these mice a Western diet for 16 weeks. We isolated and enriched mouse aortic endothelial cells with CD31 beads to perform single-cell RNA-seq. Cells populated 15 major clusters after integrating the single-cell transcriptomic profiles. In the EC-iCD45KO group, the population of endothelial, resident macrophage, and mesenchymal-endothelial transition cells increased while vascular smooth muscle, EndMT, and fibroblast cells decreased. In EndMT cells, EC markers (Cdh5, Cldn5, Pecam1) increased, but SMC markers (Acta2) and EndMT markers (Col1a2 and Col3a1）decreased. In addition, we characterized EndMT cells into two sub-clusters: 1 and 2. EC-specific CD45 deletions reduced the cell numbers in the EndMT2 sub-cluster in atherosclerotic mice but had less impact on the EndMT1 sub-cluster. FGFR pathways were potentiated while TGFβ1 and Tgfbr2 decreased in EndMT1 sub-cluster， and the genes controlling endothelial cell development were upregulated but the genes controlling actin cytoskeleton organization were downregulated in both EndMT1 and 2 sub-clusters. Conclusion: Our single-cell analysis indicates that the loss of endothelial CD45 protects against EndMT-driven atherosclerosis, inhibiting TGFβ and EndoMT marker expression while stimulating FGFR pathways. Consistently, EC-iCD45KO/ApoE -/- mice showed reduced plaque macrophages, expression of cell adhesion molecules, foam cell formation, and lesion development when compared to ApoE -/- controls. Thus, targeting endothelial CD45 may be a novel therapeutic strategy for EndMT and atherosclerosis.
Abstract 4118070: High Output Heart Failure After Leadless Pacemaker Placement In a Heart Transplant Recipient
Authors: Han Wool Kim, Paris Malensek, Robert Morlend, Hadi Beaini, Ravi Patel, Patrick O'Hara, Montana Goral, Fizza Hussain, Maryjane Farr, Faris Araj
Journal: Circulation (2024)

Introduction: The advent of leadless pacemaker (LP) technology has revolutionized cardiac rhythm management by minimizing risks associated with traditional transvenous pacemakers. LP use is expected to increase as dual-chamber LP systems emerge into clinical practice. The LP requires a large-bore venous sheath (27-Fr) through a femoral vein. One risk of large bore femoral cannulation is creation of an occult arteriovenous fistula (AVF), which can cause high output heart failure (HOHF) over time. In the LEADLESS II trial, the event rate for AVF was 0.2%. HOHF as a complication of LP implant has not been previously reported. We describe the first case of HOHF in a heart transplant (HT) recipient after LP. Case Presentation: An 82-year-old male with a history of HT 26 years earlier underwent leadless pacemaker for recurrent syncope, deemed associated with conduction system disease. He had no history of cardiac allograft rejection, angiographic coronary allograft vasculopathy or left ventricular dysfunction. Six months post-implant he presented with shortness of breath and bilateral lower extremity edema. Management: Evaluation included: 1) Chest X-ray which was suggestive of pulmonary edema 2) natriuretic peptide level of 5,500 pg/ml (6-fold increase from 6 months prior) 3) echocardiogram showing EF of 69%, and 4) bilateral lower extremity Doppler ultrasound where he was found to have a large AVF between the right superficial femoral artery and superficial femoral vein. Subsequent right heart catheterization was notable for a PCWP of 18 mmHg and a cardiac output/index of 11 L/min and 5.8 L/min/m2 respectively, hence confirming HOHF. Treatment with intravenous diuretic was initiated and percutaneous stent placement to correct the AVF was performed with symptomatic relief. Conclusion: This case highlights the rare but serious complication of unrecognized AVF following leadless pacemaker implant. Given that this event occurred in a HT recipient, a more exhaustive work-up was required to rule-out expected causes of congestion. To our knowledge there is only one other case report describing AVF post-LP implant for which no intervention was performed due to absence of symptoms at 6-month follow up and HOHF was not reported. Our case emphasizes that the differential diagnosis of new onset of signs and symptoms of heart failure that develop post LP implant in general and in HT recipients specifically, should include HOHF related to an unrecognized procedural AVF.
Abstract 4113164: Central Arterial Stiffness in Young Adults with Perinatal HIV Exposure
Authors: Elaine Urbina, Wendy Yu, Paige Williams, George Sawyer, Russell Van Dyke, Steven Colan, Steven Lipshultz
Journal: Circulation (2024)

Intro: Young adults with perinatally acquired HIV (YPHIV) have higher morbidity and mortality than uninfected persons. Antiretroviral therapy (ART) has extended life expectancy making adult CV disease a concern. Perinatal exposure to HIV increases inflammation which is associated with increased arterial stiffness which predicts CV disease. Aims: We compared arterial stiffness between YPHIV and young adults perinatally HIV exposed but uninfected (YPHEU), and evaluated the association of type and duration of ART regimens, HIV disease severity, and cardiac structure and function with arterial stiffness. Methods: In a substudy of the Pediatric HIV/AIDS Cohort Study, 150 participants (95 YPHIV, 55 YPHEU, mean 23.4 yrs, 60% female, 72% Black, 24% Hispanic) had echocardiography and pulse wave velocity (PWV) measured. We compared PWV between YPHIV and YPHEU, adjusting for covariates. Among YPHIV, we fit linear regression models to evaluate the association of current (within 1 year of PWV) and historical measures of HIV disease severity with PWV. We computed correlations between PWV and measures of left ventricular (LV) structure and function, overall and by HIV status. Results: Mean PWV and hemodynamic parameters did not differ between YPHIV and YPHEU (YPHIV 5.63 vs YPHEU 5.39 m/s; p=0.5). HIV control was good (82% with viral load &lt;400 copies/ml), 91% used combination ART: integrase strand inhibitors (INSTIs; median duration 4.6 years), protease inhibitors (PIs 15.1 years), or non-nucleoside reverse transcriptase inhibitors (NNRTIs 5.2 years). Most participants had normal PWV compared to healthy controls but all values above 11.8 m/sec ( Figure , level associated with CV events in adults) were only in YPHIV. Only weak correlations were observed between PWV and echocardiographic measures (&lt;0.20) in both YPHEU and YPHIV. Among YPHIV, HIV severity measures were not associated with PWV using either current or historical measures. Mean PWV was 1.68 (-0.36, 3.72) m/s higher among YPHIV with current PI use than those on INSTIs, and 1.58 (-0.94, 4.11) m/s higher than those on NNRTIs, although these differences were not significant. Conclusions: PWV was within normal ranges in most YPHIV and YPHEU although 5% YPHIV had elevated PWV. PWV may be higher with PI use due to cardiometabolic side effects. Successful HIV treatment and control of traditional CV risk factors may prevent premature vascular aging and subsequent cardiac compromise in YPHIV.