tbuckley/cabot-search huggingface dataset:
Abstract 4146929: Comparison of Right Ventricular Dysfunction Following Catheter-Directed, Half-Dose, and Full-Dose Thrombolysis for Acute Pulmonary Embolism
Authors: Simran Koura, Quinn Mallery, Jacob Clarke, Frances Greathouse, Myoung Hyun Choi, FNU Riya, Elizabeth Bruno, Punit Arora, Waddah Malas, Parth Shah, David Sutherland, Amudha Kumar, Igor Wroblewski, Amir Darki
Journal: Circulation (2024)

Introduction: Systemic thrombolysis (ST) is the mainstay of treatment for acute massive pulmonary embolism (PE). Catheter directed therapy (CDT) has become more common in treatment of acute PE in patients with contraindications to ST. Half-dose ST (hdST) has also been utilized with similar efficacy and a lower risk of bleeding than full-dose ST (fdST). It is uncertain how right ventricular dysfunction (RVD) on transthoracic echocardiography (TTE) varies comparing all three modalities. Research Question: How does RVD on TTE imaging in acute PE vary based on the thrombolytic modality? Methods: We conducted a retrospective, multi-center cohort study using data from our institutional PE Response Team registry. TTE imaging was directly assessed to obtain parameters. Included patients were over 18 years old with TTE’s obtained after CDT, fdST, or hdST, excluding those missing key RVD parameters (TAPSE, S', RV ratio, RVOT VTI, RVOT notching, 60-60 sign). RVD was defined as threshold values met in two or more parameters. Between group univariate testing was performed using ANOVA, Student’s t-test, chi-squared, and Fisher’s exact test when appropriate for the entire cohort as well as specifically CDT vs. hdST. Results: The final cohort included 188 patients, with 163 undergoing CDT, 19 receiving hdST, and 6 receiving fdST. Patients with hdST had significantly higher RVOT VTI (13.8 ± 5.7 cm) compared to the CDT group (10.7 ± 4.5 cm, p=0.016). There were lower rates of RVD in the hdST group (26.3%) compared to CDT (39.3%, p=0.04). Bleeding rates were not statistically different across all three cohorts (p=0.78) Conclusion: Despite the higher severity of illness on presentation, patients treated with hdST had lower rates of RVD following treatment compared to those treated with CDT, without increased rates of bleeding. Further investigation is needed; however this study provides additional evidence supporting the safety of hdST in hospital systems lacking access to CDT.
Abstract 4147376: Leveraging Telemedicine to Assess Care Quality Among Rural-Residing Patients with Heart Failure: The Rural-HF Registry
Authors: James Miller, Neil Keshvani, Pritam Ghosh, Chris Gallagher, Katherine Sanchez, Javed Butler, Ambarish Pandey
Journal: Circulation (2024)

Introduction: Heart failure (HF) poses a major public health challenge in the United States, and patients in rural areas experience worse HF outcomes. Telemedicine has effectively provided access to specialty cardiovascular care to hospitalized patients in rural hospitals. A better understanding of care quality among patients hospitalized with HF in rural hospitals is needed to improve outcomes in this vulnerable population. Methods: We developed a virtual registry of patients hospitalized with acute HF in rural hospitals in collaboration with the American Heart Association (Grant: 23DSG1154425) and Access Telecare, a nationwide telehealth provider. Patients hospitalized to 13 rural hospitals across Texas, Indiana, South Carolina, and New Mexico are prospectively enrolled. Patients with acute HF are identified with an ICD 10 code for HF in the primary or first secondary position. Demographics, in-hospital care, post-discharge follow-up, and discharge utilization of GDMT (renin-angiotensin-aldosterone inhibitors (RAASi), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter-2 inhibitors (SGLT2i) for HFrEF; RAASi, MRA, SGLT2i for HFpEF) were abstracted from the electronic medical record. Results: As of June 6, 2024, 254 patients (mean age 72 y, 40.2% female, 7.5% Black) were included (Table). 42.1% had HFrEF. 37% underwent LVEF assessment during the hospital stay. 74.4% of all patients received any GDMT at any dose, 4.7% received all classes of GDMT at any dose, and only 1.2% were prescribed GDMT at optimal doses. Among patients with HFrEF, evidence-based (vs non-evidence-based) BB was 58.9% and 15%, respectively. Furthermore, 74.7% of patients with HFrEF received ≤ 2 GDMT classes. At discharge, 0.4% of patients were referred for cardiac rehabilitation and 41.3% had a follow-up visit scheduled. Among patients with a history of atrial fibrillation/flutter, the rate of anticoagulation was 57.3%. Conclusion: There are considerable implementation gaps in GDMT and post-discharge care for patients with HF hospitalized in rural areas. Effective and scalable telemedicine interventions are needed to improve the uptake of GDMT among hospitalized HF patients in rural areas.
Abstract 4147227: TET2-mediated Clonal Hematopoiesis Exacerbates Foam Cell Generation
Authors: Shaunak Adkar, Shaneice Mitchell, Mozhgan lotfi, Yoko Kojima, Sabina Sorondo, Lingfeng Luo, Changhao Fu, Caitlin Bell, Siddhartha Jaiswal, Derek Klarin, Nick Leeper
Journal: Circulation (2024)

Introduction: Clonal Hematopoiesis of Indeterminate Potential (CHIP) is associated with atherosclerotic cardiovascular disease (ASCVD) and is often caused by somatic mutations in the epigenetic modifier TET2. Reduced TET2 causes ASCVD through increased inflammatory signaling in tissue macrophages. Recently, macrophage lipid loading has been shown to potentiate inflammatory activation, particularly in the context of TET2 deficiency. Therefore, we sought to test the hypothesis that TET2 deficiency exerts a proinflammatory phenotype by directly increasing macrophage lipid uptake. Methods: Using CRISPR/Cas9 genome editing, we modeled TET2-CHIP through monoallelic disruption of the TET2 open reading frame in THP-1 monocytes (TET2 +/- ). We targeted the AAVS1 safe harbor locus to generate mock-edited control lines (AAVS1 +/- ). After differentiation to macrophages, we assayed uptake of phrodo-labeled low density lipoprotein (phrodo-LDL) using live cell imaging and fluorescently conjugated oxidized LDL (DiI-oxLDL) using flow cytometry. RNA-sequencing libraries were constructed from TET2 +/- and AAVS1 +/- lines treated with or without oxLDL. Differentially expressed genes (DEGs) were identified with DESeq2. Pathway analysis was conducted using clusterProfiler. We used publicly available CHIP-seq data to assay TET2 binding at ENCODE candidate cis-regulatory elements (cCREs). Results: We observed a two-fold increase of phrodo-LDL uptake in TET2 +/- cell lines compared to controls over a 24 hour period (p &lt; 0.05). TET2 +/- lines treated with DiI-oxLDL exhibited significant increases in both mean fluorescence intensity (9774 vs. 7954, p &lt; 0.001) and proportion of DiI + foam cells (81.7% vs. 74.7%, p &lt; 0.05). Compared to controls, TET2 +/- lines had four-fold increased expression of inflammatory cytokine CCL5 with and without oxLDL stimulation (p&lt;0.001). The most significantly upregulated genes in TET2 +/- lines treated with oxLDL were VDLR (3.7-fold, p &lt; 0.001) and LDLR (9-fold, p&lt;0.001). Pathway analysis revealed significant enrichment of KEGG term ‘IL-17 signaling’ in ox-LDL treated TET2 +/- lines (p&lt;0.001). CHIP-seq revealed TET2 occupancy at an LDLR cCRE. Conclusion: We demonstrate that TET2 deficiency stimulates foam cell formation through increased LDL and oxLDL uptake, possibly due to aberrant activation of LDLR and VLDLR. These data suggest that therapeutic approaches targeting lipid metabolism may have an outsized benefit for patients with TET2 CHIP.
Abstract 4147275: A Longitudinal 20-year Analysis Indicates Acceleration of Cardiometabolic Comorbidities on Dementia Risk
Authors: Lihua Huang, Muhammad Danish, Tung Wai AuYeung, Jenny Lee, Timothy Kwok, Jill Abrigo, Yingying Wei, Cecilia Lo, Erik Fung
Journal: Circulation (2024)

Background: Dementia often seen in people aged ≥65y years is a major public health burden in Hong Kong, as its men and women have one of the longest lifespan worldwide. Using territory wide electronic health records (EHRs) spanning &gt;20 years, we investigated the impact of cardiometabolic comorbidities on dementia risk. Methods: EHRs of public hospitals provided by Hong Kong’s Hospital Authority (HADCL) were examined for patient visits from 01/01/2000 to 12/31/2020. Included were individuals born in 1920,1930,1940,1950 with ICD-10 codes for all-cause dementia, or use of dementia and/or psychotropic drugs. Atrial fibrillation, stroke, hypertension, myocardial infarction, diabetes mellitus, chronic kidney disease, and hyperlipidemia identified by ICD codes or dispensed diabetic drug(s) or dihydropyridine calcium channel blocker (for hypertension) were investigated for age-dependent association with dementia using landmark analysis with multivariate Cox models. Results: A total of 222,418 patients (49% female) in four birth cohorts were examined with landmark analysis, which showed similar incidences for dementia. Adjusted for multiple testing, increased risk of all-cause dementia stratified by birth cohorts were significantly associated with hypertension and stroke from age 65, diabetes from age 50, and chronic kidney disease among men from age 58–64 (Figure). Earlier onset of these comorbidities except for hypertension were associated with increased dementia risk. Moreover, while the risk of dementia declined with old age in patients with diabetes, the risk for dementia markedly increased with hypertension after age 80. Surprisingly, the most recent birth cohorts, especially males, showed dementia risk elevation with diabetes, stroke and chronic kidney disease. Conclusion: We showed hypertension is a major risk for dementia in men/women &gt;80 years, indicating hypertension management is critical for dementia risk reduction in the aged. The increase in dementia risk with stroke, diabetes, and chronic renal disease in the recent birth cohorts indicates disease burden acceleration predicting increase in economic burden. Further studies are warranted to investigate possible epigenetic mechanisms modulating dementia risk.
Abstract 4147117: Impact of Heavy Metal Exposure On Cardiovascular Disease Mortality
Authors: Hafiz Muhammad Waqar Younas, Harshith Thyagaturu, Muchi Ditah Chobufo, Kunal Patel, Hardik Valand, Dipesh Ludhwani, Vikram Padala, Hafiz Khizer Mubeen, Prakash Upreti, Hafiz Muhammad Umair Younas, Karthik Gonuguntla
Journal: Circulation (2024)

Background: Cardiovascular disease (CVD) is the primary cause of mortality worldwide, and heavy metal exposure, including lead (Pb), cadmium (Cd), and mercury (Hg), significantly impacts this global burden of disease. Heavy metal-related cardiovascular toxicity results from their ability to induce oxidative stress, inflammation, endothelial dysfunction, and dysregulation of lipid metabolism. We aim to investigate the cardiovascular disease mortality associated with high blood levels of Pb, Cd, and Hg. Method: Using the 1999–2018 National Health and Nutrition Examination Survey (NHANES) data, we examined the association of blood Pb, Cd, and Hg levels with CVD mortality. Pb, Cd, and Hg levels were transformed into quartiles. Mortality hazard ratios were calculated using Cox proportional multivariate regression models adjusting for confounders identified by way of univariate analysis and from literature. Survival across quartiles of Pb, Cd, and Hg levels are depicted using K-M curves. Survival probabilities were compared using KM curves. All analyses were conducted using STATA version 17.0 Results: The study population comprised 55,081 participants spanning over 20-years period, among whom 2401 (4.36%) experienced CVD related to Pd, Cd, and Hg exposure. Of the participants, 48% were male, with the majority being White participants, followed by Hispanic and Black participants. Most participants (82.4%) had a college education or higher, 53.2% were from high-income families, and 91.3% did not report a history of CVD. Mean levels of Pb, Cd, and Hg were 0.51 µg/L, 1.62 µg/L, and 1.56 µg/L, respectively. Significant differences in CVD mortality were observed between the toxic metal exposure group and those without exposure. The mortality group was associated with a higher prevalence of diabetes, higher BMI, CVD history, and higher levels of Cd and Pb but lower Hg levels. Conclusions: In conclusion, our study revealed a higher prevalence of cardiovascular mortality in individuals with elevated blood Pb and Cd levels. In contrast, those with higher blood Hg levels exhibited reduced cardiovascular mortality
Abstract 4147213: Does Well-Controlled, Recent-Onset Diabetes Increase Stroke Hazard in Atrial Fibrillation? A Population-Based Cohort Study
Authors: Madison Gunn, Yue Chen, Anna Chu, Jiming Fang, Husam Abdel-Qadir
Journal: Circulation (2024)

Introduction: Stroke prevention with anticoagulation is an important aspect of atrial fibrillation (AF) management. Anticoagulation is often based on the premise that the risk of stroke increases with each additional CHA2DS2VASc risk factor. Diabetes is accepted as a risk factor for stroke in AF, but the threshold at which stroke risk increases is uncertain. Specifically, it is unknown if AF patients with recent-onset well-controlled diabetes (ROWCD) are at increased risk of stroke in AF compared to AF patients without diabetes. Hypothesis: We hypothesize that patients with AF and diabetes of &lt;5 years’ duration with glycated hemoglobin (HbA1c) ≤7% who do not use insulin (henceforth designated as the ROWCD group) do not have a significantly different adjusted hazard of stroke than AF patients without diabetes. Methods/Approach: Using linked administrative databases in Ontario, Canada, we conducted a population-based retrospective cohort study of patients ≥66 years who had a new AF diagnosis between Apr 1 2013 and Mar 31 2022. Exclusion criteria included insulin use. Cause-specific hazard regression was used to quantify the adjusted hazard ratio (HR) for stroke over 2 years of follow-up in patients with AF plus diabetes relative to AF patients without diabetes (adjusting for baseline stroke risk factors and time-varying anticoagulation status). The analysis was repeated after excluding people with diabetes of ≥5 years duration, HbA1c &gt;7%, or missing HbA1c data (to generate the ROWCD subset). Results/Data: The primary analysis included 233,692 patients with AF (mean age 78.8 years, 50.9% male), of whom 64,972 (27.8%) had diabetes. Diabetes was associated with an adjusted HR of 1.15 (1.08-1.22) for stroke in the full cohort (p&lt; 0.001). After excluding people with diabetes of ≥5 years duration, HbA1c &gt;7% or missing HbA1c, there were 7,415 patients with ROWCD. Mean diabetes duration was 3.0 years, mean HbA1c was 6.2%, with 38.5% metformin use, 10.6% dipeptidyl peptidase-4 inhibitor use, and 5.3% sulfonylurea use. There were 3,503 (2.1%) strokes in the non-diabetes group and 139 (1.9%) in the ROWCD group. ROWCD was not significantly associated with adjusted stroke hazard (HR 0.96, 95% CI 0.81-1.13, p=0.61). Conclusions: These findings suggest that people with AF who have ROWCD may not warrant a point on the CHA2DS2VASc score, as this subset of diabetes is not associated with increased hazard of stroke in AF.
Abstract 4147770: TAVR versus SAVR for Severe Aortic Stenosis in the Low and Intermediate Surgical Risk Population: A Meta-Analysis of Randomized Controlled Trials
Authors: Mrinal Murali Krishna, Meghna Joseph, Chidubem Ezenna, Vinicius Pereira, Andrew Goldsweig
Journal: Circulation (2024)

Background: Randomized control trials (RCTs) have compared transcatheter aortic valve replacement (TAVR) with surgical aortic valve replacement (SAVR) for patients with severe aortic stenosis (AS) at low-intermediate surgical risk. Objective: To compare TAVR vs. SAVR for AS in low-intermediate surgical risk patients. Methods: We systematically searched PubMed, Scopus, and Cochrane Central databases for studies comparing TAVR with SAVR for AS in low-intermediate surgical risk. Outcomes included composite death or stroke, death, stroke, myocardial infarction (MI), cardiac death, new atrial fibrillation (AF), new pacemaker implantation, acute kidney injury (AKI), bleeding, major vascular complications, endocarditis, aortic valve reintervention, and rehospitalization at 1 year. Random effects models were used to generate risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I 2 statistics. Results: The systematic review identified 8 RCTs including 9,239 patients (TAVR n=4,695, 50.8%). Death or stroke (RR 0.78; 95%CI 0.62-0.98; p=0.033; I 2 =52%), cardiac death (RR 0.79; 95%CI 0.63-0.98; p=0.029; I 2 =1%), bleeding (RR 0.39; 95%CI 0.25-0.60; p&lt;0.001; I 2 =94%), new AF (RR 0.28; 95%CI 0.20-0.40; p&lt;0.001; I 2 =83%), and AKI (RR 0.50; 95%CI 0.35-0.70; p&lt;0.001; I 2 =0%) were lower with TAVR. New pacemaker implantation (RR 2.25; 95%CI 1.50-3.39; p&lt;0.001; I 2 =86%) and aortic valve reintervention (RR 1.95; 95%CI 1.19-3.20; p=0.008; I 2 =0%) were higher with TAVR. Death, stroke, MI, major vascular complications, endocarditis, and rehospitalization were comparable. Conclusion: In low-intermediate surgical risk patients, TAVR carries a lower risk of major adverse outcomes than SAVR.
Abstract 4147246: Establishing Correlation of Non-Invasive Monitoring Techniques in Xenotransplantation
Authors: Sarah Cipriano, Muhammad Mohiuddin, Andrew Tully, Javier Galindo, Susie Hong-Zohlman, Marco Oldsman, Albert Hicks, Timm Dickfeld, Anuj Gupta, Alison Grazioli, Allison Lankford, Erika Feller, Bartley Griffith, Manjula Ananthram
Journal: Circulation (2024)

Introduction: Non-invasive s urveillance of cardiac allograft health has included biomarkers such as NT-proBNP, and donor-derived cell-free DNA (dd-cfDNA). It has previously been shown that these biomarkers when elevated, indicate graft complications such as rejection, coronary artery vasculopathy, or donor-specific antibody production. As xenotransplantation enters the arena as a potential option for those with advanced heart failure, noninvasive monitoring techniques need to be investigated. Our institution performed the second porcine to human cardiac xenotransplant with a 10 gene edited porcine cardiac xenograft under FDA compassionate use authorization. After requiring perioperative transfusions, by post operative day (POD) 13, endomyocardial biopsy (EMB) revealed antibody and complement deposition without damage. Hemodynamic decompensation on POD 29 prompted EMB, revealing antibody mediated rejection (AMR). Research Questions/Goals: The authors sought to investigate if NT-proBNP and dd-cfDNA positively correlate in the patient with cardiac xenograft. Methods/Approach: NT-proBNP was checked periodically and dd-cfDNA was assessed once to twice weekly post-transplant. A retrospective review was completed including Pearson’s correlation coefficient analysis. Results/Data: There was a weak negative correlation between the NT-proBNP and dd-cfDNA (r=-0.28). After the initial spike in the perioperative period, NT ProBNP levels declined. NT Pro-BNP did not rise as dd-cfDNA did at the time of biopsy proven antibody mediated rejection (AMR). See the graphic below for details Conclusion: Noninvasive surveillance of cardiac xenografts needs further investigation. Biomarkers such as NT-proBNP negatively correlated with dd-cfDNA, which increased as expected at the time of biopsy proven antibody mediated rejection. Porcine xenografts are accustomed to a low-pressure circulatory system in contrast to the human recipient milieu. Despite this increased load to the xenograft, NT-proBNP levels decreased significantly after the initial postoperative phase. The NT proBNP values could have been lower than expected due to the effects of continuous renal replacement therapy. It is interesting to also note that the human assay detected xeno NT-proBNP.
Abstract 4147395: Peanut Induced Myositis: The Adversity from Overconsumption of Omega 6 Fatty Acids
Authors: Ayesha Samad, Michael Rothberg, Riddhi Machchhar, Lee Manchio, Andrea Marin, Syed Ali, Yash Shah
Journal: Circulation (2024)

Background: Peanuts, a heart-healthy staple due to their high polyphenolic antioxidant content, contain a substantial amnount of omega 6 fatty acids. An excess of the Omega-6 polyunsaturated fatty acids (PUFAs), up regulates the body’s inflammatory pathways.The n-6 PUFA-derived lipid mediators trigger inflammation, platelet aggregation, and vasoconstriction. Omega 3 fatty acids in foods such as salmon or avocado, inhibit inflammation and platelet aggregation while enhancing vasodilation. Over consumption of omega 6 fatty acids by more than the 5-10% daily recommendation can lead to inflammatory conditions like myositis, as seen in this case presentation. Case Presentation: A 70-year-old Caucasian male presented to his primary care clinic for worsening bilateral lower extremity myalgias for the past few months. His medical history includes hypertension, non-insulin- dependent type 2 diabetes, and hyperlipidemia. He denied any trauma, strenuous exercise, myocardial infarction, or mechanical falls. His home medications were aspirin, low-dose Crestor, Pioglitazone, Janumet, and Farxiga. Radiographic imaging of the lower extremities was unremarkable. He had elevated creatinine kinase (CK) levels from 2018-2022, ranging from 300-500’s. A trial withholding the statin (Crestor), was initiated to check for improvement, but serum creatinine levels remained high. His muscle biopsy was unrevealing as well. During an office visit in 2022, the patient incidentally stated he had been eating a one-pound bag of shelled peanuts daily for the lat 4 years to improve his health. He was advised to eliminate peanuts for a month and have a follow up CK level testing. Results: The creatinine kinase levels between 2018-2022 revealed a baseline elevation until May 2022 when the patient returned for an office visit after abstaining from peanuts for a month. His CK levels not only normalized in May 2022, but also coincided with resolution of his myalgias. These results reveal the association between over consumption of omega 6 fatty acids as a trigger for myositis. Conclusion: The patient was educated on the detrimental health effects from over consumption of omega 6 fatty acids and the importance of moderation in the diet. This case illustrates the link between omega-6 fatty acid as a precursor to inflammatory disease. The patient's peanut consumption being the culprit of his myositis also highlights the importance of good history taking and exploring diet as a conduit to disease management.