tbuckley/cabot-search huggingface dataset:
Abstract 13999: The Relationship Between Neighborhood Deprivation, Diabetes, and Extracellular Vesicles in African American Women at Risk for CVD: Data From a Pilot Study of the Step It Up Physical Activity Intervention
Authors: Yvonne Baumer, Noel Miller, Matthew Bavuso, Nithya Vijayakumar, Sam Neally, Kameswari Potharaju, Joniqua N Ceasar, Kaveri Curlin, Marcus Andrews, Briana Turner, Cristhian Gutierrez Huerta, James Troendle, Valerie Mitchell, Billy Collins, Maureen Sampson, Alan Remaley, Anca Dobrian, Tiffany M Powell-Wiley
Journal: Circulation (2023)

Background: African American women (AA) are at disproportionally high risk for diabetes and cardiovascular disease (CVD) which is accelerated when residing in resource-limited neighborhoods. Extracellular vesicles (EV) are emerging to be of importance in CVD development and progression, but little is known about a potential impact of neighborhood socioeconomic deprivation (NSD). In this study we examined associations between NSD, plasma EV, and markers of diabetes risk in a community-based cohort of AA women at risk for CVD from resource-limited neighborhoods in Washington, DC. Methods: Participants were enrolled in pilot testing of Step It Up, a community engaged physical activity intervention. Blood samples were drawn to measure clinical labs during participants’ baseline visit to the NIH Clinical Center. EV were isolated from heparinized plasma using size exclusion chromatography with size and numbers determined by nanoparticle tracking analysis. NSD was calculated using 2018 US Census tract data as a measure of neighborhood deprivation. Associations between NSD, EV, and diabetes-related clinical measures were analyzed using multivariable regressions adjusted for BMI and ASCVD 10-year risk score. Results: The study cohort was a convenience sample of AA women at risk for CVD (N=24, Age: 57±12, BMI: 35±6, ASCVD: 9±5). NSD associated with fasting glucose (β=0.54, p=0.007) and Hemoglobin A1c (HA1c) (β=0.51, p=0.007). Additionally, NSD associated with lower EV size (β=-0.42, p=0.03), with no association with EV concentration. Fasting glucose and HA1c associated negatively with EV size (β=-0.48, p=0.03 and β=-0.50, p=0.02, respectively) but no association was found with EV concentration. Conclusions: Thus, our data show that higher neighborhood deprivation is associated with lower EV size which, in turn, is associated with higher diabetes risk markers. More research is needed to understand the role of EV in diabetes and CVD development and progression. While larger studies further evaluating these observations are needed, our data highlight the importance of increased diabetes screening and multi-level interventions in patients residing in under-resourced communities to reduce existing health disparities.
Abstract 14742: Clinical Predictors of Bleeding Complications Following Percutaneous Ventricular Assist Device Insertion: Insights From the J-PVAD (Japanese Registry for Percutaneous Ventricular Assist Device) Registry
Authors: Madoka Sano, Toshiaki Toyota, Ryosuke Murai, Taiji Okada, Yasuhiro Sasaki, Tomohiko Taniguchi, Junichi Ooka, Kitae Kim, Atsushi Kobori, Natsuhiko Ehara, Makoto Kinoshita, Yutaka Furukawa
Journal: Circulation (2023)

Introduction: Bleeding complications are significant concerns in clinical use of percutaneous ventricular assist devices (PVAD). This study aimed to identify predictors of bleedings in PVAD use. Methods: We analyzed 3059 cases from the J-PVAD registry, a comprehensive national registry of PVAD use in Japan, excluding 53 cases without follow-up data. Patients were stratified based on whether they had acute coronary syndrome (ACS) on the onset or not, and incidence of bleeding was evaluated within each stratum, considering the clinically selected variables, including other mechanical circulatory support (MCS) use. Risk factors were explored through multivariate analyses. The primary outcome measure was any bleeding, while major bleeding was defined as a composite of cerebral bleeding, severe bleeding (defined as life-threatening, hospitalization-requiring, disability-causing, or congenital anomaly-inducing bleeding events), and blood transfusions. Results: The median follow-up period was 32 days. The cohort included 1459 patients with ACS and 1575 without ACS. The incidence of any bleeding did not differ significantly between the ACS and Non-ACS stratum (30-day incidence: 25.4% and 27.6%, P = 0.57, respectively). We observed the same trends for major bleeding. Most any bleeding or major bleeding occurred on the day of insertion of PVAD or within a few days. The groups with MCS had significantly more bleeding complications than those without MCS in each stratum (Figure). In a multivariate analysis using the Cox proportional hazards model, adding MCS on PVAD was the most potent predictor of any bleeding in both strata, with the effects of other variables being modest by comparison. Conclusions: Bleeding complications post-PVAD insertion are often severe and occur shortly after the procedure. Although the incidence of bleeding complications did not differ significantly according to the onset type, the MCS use strongly predicted bleeding complications.
Abstract 14234: Fast Track Use of PCSK9i in Acute Coronary Syndromes in Real World Practice. Insights From the AT-TARGET-IT Registry
Authors: Christian Basile, Paola Gargiulo, Federica Marzano, Angelo Catalano, Giuseppe Musumeci, Gennaro Galasso, Marco M Ciccone, PAOLO CALABRO', saverio muscoli, FERDINANDO VARBELLA, Piera Angelica Merlini, Leonardo De Luca, Ciro Indolfi, Mario Crisci, Natale D Brunetti, Italo Porto, Leonardo Paloscia, Stefania Paolillo, Pasquale F Perrone Filardi
Journal: Circulation (2023)

Introduction: In patients with recent acute coronary syndrome (ACS), PCSK9 inhibitors (PCSK9i), alirocumab and evolocumab, intensively decrease LDL-C and determine reduction of ischemic events. Yet, scant data are available on the initiation of PCSK9i in ACS patients in real-world setting. Aim: AT-TARGET-IT is an Italian multicenter prospective phase 4 registry involving 23 centers, designed to assess efficacy, safety and adherence of PCSK9i, as well as clinician’s behavior on lipid lowering therapies (LLT) in patients at very high CV risk. Aim of the current analysis is to report efficacy and safety in patients suffering ACS who received early prescription of PCSK9i during hospital stay, according to national reimbursement rules. Methods: From March 2020 through May 2023, we enrolled patients receiving PCSK9i as part of their optimal medical therapy. Clinical, laboratory and demographic characteristics and concomitant therapies were recorded at the time of first prescription and in subsequent follow-up. Results: We report 405 patients (22% female, age 61 years, 60% chronic coronary syndromes). Median LDL-C was 142 mg/dL at hospital admission, reached 45 mg/dL at first control (time 37 days, 67% reduction, 97 mg/dl absolute reduction) and remained unchanged at latest lipid control (time 11 months, 66% reduction, 94 mg/dl absolute reduction). Of 405 patients enrolled, 252 patients (62%) were receiving LLT at time of hospital admission, of them 91 (36%) were on ezetimibe, 48 (19%) on statin and 113 (45%) were on a statin and ezetimibe combination. LDL-C target according to the ESC guidelines was reached in 272 patients (67%), with differences based on LLT (Figure 1-A). Also LDL-C percentage reduction was influenced by background LLT (Figure 1-B). No serious adverse reactions were reported. Conclusions: Early PCSK9i administration effectively reduces LDL-C in ACS patients in the real-world setting. However, concomitant LLT is needed to optimize early LDL.values.
Abstract 13577: Burden of Cardiometabolic Risk Factors and Vascular Health
Authors: Carine Hamo, Maria Florencia Schlamp, Kamelia Drenkova, Manila Jindal, Maja Fadzan, Adedoyin Akinlonu, Ira J Goldberg, Michael Garshick, Jeffrey Berger
Journal: Circulation (2023)

Introduction: Cardiometabolic risk factors (diabetes, obesity, and hypertension) are highly prevalent and contribute to cardiovascular disease (CVD). Endothelial dysfunction often precedes CVD development. Direct brachial vein endothelial cell (EC) harvesting enables the examination of vascular health via assessment of EC gene expression. Hypothesis: We hypothesized that individuals with greater cardiometabolic risk would demonstrate a more pro-inflammatory EC transcriptome. Methods: Adult participants without CVD underwent EC harvesting followed by RNA sequencing. We categorized individuals by number of risk factors (hypertension, diabetes, obesity) as 0 through 3. To evaluate the association between risk factor burden and outcome transcripts, we performed multivariable linear regression, adjusting for age, sex, and race/ethnicity. Results: Among 18 individuals (mean age 47 ± 14, 44% female, and 61% white), 17%, 44%, 28%, and 11% had 0,1,2, and 3 prevalent risk factors, respectively. EC RNA sequencing revealed 588 differentially expressed transcripts (p-adj &lt;0.05) with 585 upregulated, 3 downregulated, and excellent clustering ( Fig. a, b ). Gene ontology enrichment analysis demonstrated enriched and upregulated pathways of T-cell activation (NES = 2.22, p&lt;0.001), leukocyte differentiation (NES= 2.16, p&lt;0.001), and platelet aggregation (NES= 1.66, p=0.03) and downregulated pathways of endothelial cell proliferation (NES= -1.68, p=0.03). ( Fig. c ) Select upregulated genes (log 2FC &gt;3, p-adj&lt;0.05) included VCAM1, CEACAM1, ADAM 17, and CD99L2, with a graded increase in mean normalized counts with increasing number of risk factors. ( Fig. d ) Conclusions: We demonstrate a proinflammatory, pro-adhesive, and pro-coagulant EC transcriptome associated with increased cardiometabolic risk factor burden offering insight into potential mechanisms linking cardiometabolic risk factors with the development of CVD.
Abstract 14218: Trends in Prevalence of Hypertension and Untreated Hypertension Before and During the COVID-19 Pandemic Period in Japan
Authors: Hisako Tsuji, Yohei Oishi, Yuzo Akita, Hiroyuki Sueyoshi, Ichiro Shiojima
Journal: Circulation (2023)

Background: To examine influence of the COVID-19 pandemic on blood pressure in a general population, trends in prevalence of hypertension and untreated hypertension before and during the COVID-19 pandemic period were examined. Methods: We studied subjects aged 40 to 79 who had the annual health checkup offered to adult citizens of Moriguchi city, Osaka, Japan from 2015 to 2022. Sex-specific age-standardized prevalence rates of hypertension (systolic blood pressure (BP) &gt; 140 mmHg, diastolic BP &gt; 90 mmHg, or receiving antihypertensives) and those of untreated hypertension to the WHO reference population with 95% confidence intervals (CI) were calculated. Statistically significant difference was determined by 95% CI compared to the 95% CI of the prevalence of 2015. Results: Number of subjects and trends in prevalence of hypertension and untreated hypertension with 95% CI are presented in the figure. From 2015 to 2019 (before the COVID-19 pandemic period) prevalence of hypertension and untreated hypertension did not change both in men and women. However, from 2020 to 2022 (during the COVID-19 pandemic period), prevalence of hypertension and untreated hypertension significantly increased compared to 2015, except for prevalence of hypertension in women in 2020 and that of untreated hypertension in men in 2022. Conclusions: During the COVID-19 pandemic period, higher prevalence of hypertension and untreated hypertension was observed in a general population in Japan.
Abstract 17846: Successful Treatment of Recurrent Pericarditis With Rilonacept in the Setting Of ATRA/ATO Use in Acute Promyelocytic Leukemia
Authors: Muhammad Majid, Aro Daniela Arockiam, Ankit Agrawal, Ashwin Kumar, Zachary Yaker, Sarah Mudra, Allan L Klein
Journal: Circulation (2023)

Case Presentation: A 40-year-old female was admitted for a 4-day history of recurrent left-sided pleuritic chest pain. Physical examination was pertinent for tachycardia and presence of a pericardial friction rub. Past medical history included recently diagnosed Acute Promyelocytic Leukemia undergoing active chemotherapy. Complete blood count showed leukopenia. Brain natriuretic peptide was slightly elevated at 241 pg/mL. Electrocardiogram demonstrated sinus tachycardia with diffuse ST-segment elevation and PR-segment depression (Figure 1. A). Echocardiogram showed normal biventricular function with a small posterior and lateral pericardial effusion and small pericardial effusion adjacent to the right ventricle (Figure 1. B). Cardiac magnetic resonance (CMR) imaging showed a moderate circumferential pericardial effusion and increased pericardial signal on T2 STIR imaging and late gadolinium enhancement (LGE) (Figure 1. C, D). Given the constellation of symptoms and findings, the patient was diagnosed with acute pericarditis secondary to differentiation syndrome (DS) suspected to be due to her underlying malignancy and anti-cancer treatments. She was started on aspirin and colchicine. Steroids and rilonacept were later added for incomplete treatment response. On follow-up, she was doing well. Repeat CMR demonstrated mild to moderate pericardial delayed enhancement with no edema and no pericardial effusion (Figure 1. E,F). Discussion: The presentation of DS can vary, and consensus diagnostic criteria are lacking. Cases of myopericarditis with concurrent pericardial effusions have been reported in the setting of patients undergoing chemotherapeutic treatment with differentiating agents. Management is complicated and requires multi-disciplinary care. Our case illustrates that rilonacept may be considered as an alternative to corticosteroids in the treatment of recurrent pericarditis in a patient with a hematologic malignancy.
Abstract 13052: Clonal Hematopoiesis of Indeterminate Potential Predicts Incident Cardiac Arrhythmias
Authors: Art Schuermans, Caitlyn Vlasschaert, Victor Nauffal, Md Mesbah Uddin, Tetsushi Nakao, Abhishek Niroula, Marcus D Klarqvist, Lachelle D Weeks, Amy E Lin, Seyedmohammad Saadatagah, Kim Lannery, Megan Wong, Whitney Hornsby, Steven A Lubitz, Christie M Ballantyne, Siddhartha Jaiswal, Alexander G Bick, Patrick T Ellinor, Pradeep Natarajan, Michael C Honigberg
Journal: Circulation (2023)

Background: Clonal hematopoiesis of indeterminate potential (CHIP), the age-related expansion of blood cells with preleukemic mutations, is associated with atherosclerotic cardiovascular disease and heart failure. Whether CHIP independently predicts new-onset arrhythmias is unknown. Methods: UK Biobank participants without prevalent arrhythmias were included. Co-primary study outcomes were supraventricular arrhythmias, bradyarrhythmias, and ventricular arrhythmias. Secondary outcomes were cardiac arrest, atrial fibrillation, and any arrhythmia. Associations of any CHIP (variant allele fraction [VAF] ≥2%), large CHIP (VAF ≥10%) and gene-specific CHIP subtypes with incident arrhythmias were tested using multivariable-adjusted Cox regression. Associations of CHIP with myocardial interstitial fibrosis (T1 times on cardiac magnetic resonance [CMR]) were also tested. Results: This study included 410,879 participants (CHIP: n =13,901 [3.4%]; large CHIP: n =9,197 [2.2%]). Any and large CHIP were associated with adjusted HRs of 1.11 (95%CI, 1.04-1.18; P &lt;0.001) and 1.14 (95%CI, 1.05-1.22; P &lt;0.001) for supraventricular arrhythmias, 1.09 (95%CI, 1.01-1.19; P =0.029) and 1.13 (95%CI, 1.03-1.25; P =0.011) for bradyarrhythmias, and 1.15 (95%CI, 1.00-1.33; P =0.054) and 1.22 (95%CI, 1.03-1.45; P =0.023) for ventricular arrhythmias, respectively. Associations were independent of coronary artery disease and heart failure. Associations were also heterogeneous across arrhythmia subtypes and strongest for cardiac arrest. Gene-specific analyses revealed increased risk of arrhythmias across mutations in driver genes other than DNMT3A ( Figure ) . Large CHIP was associated with 1.30-fold odds (95%CI, 1.07-1.59; P =0.009) of being in the top quintile of myocardial fibrosis by CMR. Conclusions: CHIP may represent a novel risk factor for incident arrhythmias, indicating a potential target for modulation toward arrhythmia prevention and treatment. 1
Abstract 13631: Desmoplakin Cardiomyopathy in Pediatric Patients - A Distinct, Underrecognized Cohort of Arrhythmogenic Cardiomyopathy
Authors: Nak Hyun Choi, Sara Cherny, Charles I Berul, William R Goodyer, Taylor Howard, Anna Joong, Leonardo Liberman, Eric S Silver, Chet Villa, Teresa Lee, Warren Zuckerman
Journal: Circulation (2023)

Introduction: Arrhythmogenic cardiomyopathy is a spectrum of diagnoses including the historically recognized arrhythmogenic right ventricular cardiomyopathy. More recent literature describes predominately left ventricular (LV) or biventricular (BiV) involvement. Variants in the desmoplakin ( DSP) gene commonly cause LV and BiV phenotypes, though data in children are sparse. Hypothesis: Pediatric patients (pts) with DSP mutation have predominantly LV or BiV disease and may present with early onset malignant arrhythmia. Methods: We performed a multicenter, retrospective cohort study of pts &lt;21 years with pathogenic or likely pathogenic DSP variants from 6 tertiary referral children’s hospitals. We describe clinical variation in DSP probands (PBs), the first affected family member prompting genetic testing due to clinical history, as compared to genotype-positive family members (FMs) &lt;21 years of age diagnosed by familial cascade screening. Results: We identified 34 pts; 12 (35%) were PBs and 22 (65%) were FMs. Median age at genetic diagnosis was 13.3 and 12.3 years for PBs and FMs, respectively. Four PBs had LV-predominant disease; 6 had BiV disease (table 1). The most common initial diagnosis for PBs was myocarditis and dilated cardiomyopathy. ECG abnormalities were common in PBs (75%) and included left axis deviation, inferolateral T-wave inversion, and low QRS complex amplitude. The LV ejection fraction (EF) on echo was 48% and 65% for PBs and FMs, respectively. Eight PBs underwent MRI and 6 had late gadolinium enhancement involving the LV only, while 2 had BiV involvement. Six PBs underwent ICD implantation and 2 received appropriate ICD therapy (LVEF 25% and 41%). Two PBs had cardiac transplantation. Conclusion: Pediatric DSP -cardiomyopathy has predominantly LV or BiV involvement and may be misdiagnosed as myocarditis or dilated cardiomyopathy. Probands in particular, may present with early malignant ventricular arrhythmias and significant LV dysfunction.
Abstract 12750: Three Dimensional Environment for Efficient and Large Scale Generation of Smooth Muscle Cells From HiPSCs
Authors: Akazha Green, Yuhua Wei, Lei Ye, Jianyi J Zhang
Journal: Circulation (2023)

Introduction: Smooth muscle cells (SMCs) play an important role in maintaining vascular homeostasis and the development of diseases. We assess feasibility and efficacy of differentiation human induced pluripotent stem cells (hiPSCs) to SMCs in a 3-dimension (3D). Methods: hiPSCs were cultured in shaker flasks or PBS-0.1 Vessels for 48 h. Differentiation initiated (as day 0) by culturing hiPSC spheroids in RPMI+B27 without insulin (B27-) and CHIR99021 (CHIR) for 24 h. Day 1, medium was replaced with RPMI+B27-, platelet derived growth factor β (PDGF-β), and transforming growth factor β1 (TGFβ1) for 48 h, refreshed medium on day 3 for 48 h. Day 5, differentiating hiPSC-spheroids were dissociated to single cells and cultured as monolayer in RPMI +4% FBS, PDGF-β, and TGFβ1 for 72 h. Refreshed medium day 8 for 72 h. Differentiation efficiency was determined by flow cytometry and fluorescence immunostaining. The biological function of 3D differentiated SMCs was assessed in vitro and in a mouse model of ischemic limb disease in vivo . Results: Both 3D differentiation methods efficiently differentiated hiPSCs into SMCs. Flow cytometry showed that 99.4% cells expressed smooth muscle actin (SMA), 97.9% expressed myosin heavy chain 11 (MYH11), 95.1% expressed SM22, 97.5% expressed calponin, and 97.7% expressed calveolin-3 using shaker flasks. They were 99.6% for SMA, 97.9% for MYH11, 97% for SM22, 89.6% for calponin, and 87.2% for calveolin-3, respectively, using PBS-0.1 Vessels. Mean SMC cell number obtained was 4.56 x 10 7 for shaker flasks and 5.69 x 10 7 for PBS-0.1 Vessels, respectively, which were significantly higher than hiPSCs differentiated in monolayer (5.7x10 6 ). Fluorescence immunostaining confirmed that SMCs differentiated from both methods expressed SMA, MYH11, SM22, Calponin, and calveolin-3. Differentiated SMCs migrated in scratch assay, contracted in response to U-46619, an analog of the endoperoxide prostaglandin, and formed tubular structure on Matrigel in vitro. Fluorescence angiogram imaging showed that SMC transplantation effectively induced perfusion in mouse ischemic limbs. Conclusions: Both 3D differentiation methods, using shaker flasks or PBS-0.1 vessels, efficiently differentiated hiPSCs into large scales of functional SMCs.
Abstract 13568: Proteomic Analysis Reveals Protein Alterations in Drp1 Cardiac Knockout Mice With Circadian Rhythm Disruption
Authors: Juying Qian, Ming Yin, zhangwei chen
Journal: Circulation (2023)

Introduction: Mitochondria dynamics are altered in circadian rhythm disruption, and dynamin-related protein 1 (Drp1) may be an important target. Methods: Wild-type and Drp1 cardiac-specific knockout mice were divided into normal circadian group and circadian disorder group, respectively. Normal circadian group mice were housed in a standard environment (12 hours of light/12 hours of darkness), while dark group mice were housed in a 24-hour dark environment. After 4 weeks, the cardiac tissues were analysed using Tandem Mass Tag proteomics. Differentially expressed proteins (DEPs) was identified. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Gene set enrichment analysis (GSEA) was performed to find enriched biological processes. Results: Compared with the WT/N group, the Drp1-/N group possessed a total of 176 DEPs. These proteins are widely involved in mitochondrial membrane and metabolism process. We identified several differentially expressed mitochondrial dynamics-related genes, including Drp1, using Western blotting. Compared with the WT/D group, the Drp1-/D group exhibited a total of 126 DEPs. GO and KEGG showed that the DEPs were mainly involved in response to stress, metabolic pathways. For Drp1 cKO mice, the protein changes caused by the circadian rhythm disorder were mainly concentrated in vitamin transport, complement coagulation cascades. Conclusions: This study may provide an insight into the myocardial protein changes caused by Drp1 cKO with circadian rhythm disruption, which may involve in terms such as metabolic pathways, complement coagulation, and vitamin transport.