tbuckley/cabot-search huggingface dataset:
Abstract 4124084: Nitric Oxide Releasing Bionanomatrix Gel For Dialysis Arteriovenous Fistula Maturation
Authors: Ho-wook Jun, Patrick Hwang, Maheshika Somarathna, Jun Chen, Jennifer Sherwood, Brigitta Brott, Timmy Lee
Journal: Circulation (2024)

Introduction: About 600,000 patients in the US suffer from end-stage renal disease (ESRD); more than 75% of ESRD patients undergo dialysis. Vascular access dysfunction is a major cause of morbidity and hospitalization in dialysis patients. Arteriovenous fistulas (AVFs) are considered the gold standard of vascular access for dialysis. However, about 60% of AVFs fail to mature because of early venous neointimal development and poor vasodilation and vascular wall remodeling. Therefore, to promote AVF maturation, we propose the application of a nitric oxide (NO) releasing nanomatrix gel, or ‘NO gel’, on the created AVF. The NO gel is composed of peptide amphiphiles (PA), which contain a polylysine (KKKKK) group to form NO-donating residues. In this study, we test our hypothesis that the NO gel applied at AVF can promote AVF maturation by decreasing venous intimal hyperplasia, enhancing vasodilation and vascular outward remodeling in porcine model. Materials and Methods: PA containing with KKKKK was synthesized and charged with NO to produce NO gel. For in vivo studies, AVFs in porcine were created by connecting the jugular vein and carotid artery. The NO gel was applied perivascularly over the AVF anastomosis. And the pigs were sacrifice after 35 days. AVF hemodynamics were evaluated using MRI-based computed fluid dynamics analysis. Results: We found significant decrease in neointimal hyperplasia in porcine AVFs treated with NO gel compared to the control groups. Additionally, the percentage of open lumens was significantly higher in the NO gel-treated group. It is indicated that veins in NO treated group showed less fibrosis as an less type I collagen I produced in the NO treated group than control. Also, the NO gel significantly improved hemodynamics and vascular remodeling of porcine AVFs compared to the control. Conclusion: These results suggest that the NO gel plays a crucial role in AVF maturation by reducing intimal hyperplasia and stenosis following AVF creation in a pig model. When intimal hyperplasia is reduced and the vessel is dilated, less tensile force of blood flow is applied on the arterialized vein, directing the AVF to appropriate maturation.
Abstract 4122679: Associations Between Recent and Cumulative Lifetime Cannabis Use and Sleep Health in Middle-Aged Adults: 35-Year Insights from the Coronary Artery Risk Development in Young Adults (CARDIA) and CARDIA Sleep Studies
Authors: Thanh-Huyen Vu, Kristen Knutson, Reto Auer, Julian Jakob, Donald Lloyd-Jones, Mercedes Carnethon
Journal: Circulation (2024)

Background: Cannabis use has become common, but its effects on sleep health—an important contributor to cardiovascular health—remain poorly understood. We investigated associations between recent and cumulative lifetime cannabis use and objective and subjective sleep measures in middle-aged adults. Method: We assessed recent cannabis use (last 30 days) repeatedly from young adulthood (age 18-30 at baseline in 1985-86) to middle age (after 35 years) in the longitudinal Coronary Artery Risk Development in Young Adults (CARDIA) study. Cumulative lifetime cannabis use (1 year = 365 days of use) was estimated by summing days of use during follow-up. At Year 35 (Y35), we obtained objective sleep measures (duration, efficiency, fragmentation, wake after sleep onset [WASO]) via 7-day wrist actigraphy from CARDIA Sleep Ancillary Study II. Subjective sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Robust regression models adjusted for Y35 age, sex, race, education, cumulative cigarette smoking, alcohol use, other substance use, physical activity, body mass index, sleep medication, and comorbidities. We also examined race, sex, and cigarette smoking status differences in associations. Result: Of 571 participants, mean age was 61.9 years; 65% were female, and 35% Black. Means (SD) for sleep duration, efficiency, fragmentation, WASO, and PSQI were 6.9 (1.1) hours, 90.5 (4.2)%, 20.6 (7.6)%, 43.5 (20.9) minutes, and 6.1 (3.6) scores, respectively. At Y35, 13.8% reported recent cannabis use, 56% reported former use, mean (SD) cumulative use was 1.6 (4.4) years. With adjustment, recent cannabis use was associated with longer sleep duration, lower efficiency, and higher WASO; former cannabis use was associated with longer sleep duration (Table). Compared to those with cumulative cannabis exposure years in the first quartile, fourth quartile users had longer sleep duration, lower efficiency, and higher WASO (β/p-value: 0.3/0.01, -1.2/0.01, and 8.9/&lt;.001, respectively). PSQI was not associated with recent or cumulative cannabis use. Associations were similar across race, sex, and cigarette smoking status. Conclusion: Recent and cumulative lifetime cannabis use is associated with longer sleep duration and poorer sleep quality in objective, but not subjective, measures. Further longitudinal studies are needed to identify interventions aimed at improving sleep health and promoting cardiovascular health in cannabis users.
Abstract 4123806: Early Findings on the Impact of Renin-Angiotensin-Aldosterone System Inhibitors on Bicuspid Aortic Valve Disease Progression: A Single Center Cohort Study
Authors: Ofir Brem, Elchanan Samuels, Tamir Bental, Ilan Richter, Ran Kornowski, Rafael Hirsch, Guy Witberg, Nili Schamroth Pravda
Journal: Circulation (2024)

Introduction: Patients with a bicuspid aortic valve (BAV) often have an associated aortopathy, increasing their risk of aortic dissection. Currently, there is no proven therapy to stabilize the growth of BAV aortopathy. This study aimed to assess the effect of cardioprotective medications, specifically renin-angiotensin-aldosterone system inhibitors (RAASi), on the progression of aortic dilation in adult BAV patients. Methods: A retrospective cohort study was conducted including adult patients with BAV followed at our center between 1996-2020. All patients had echocardiography imaging with at least 5 years of follow-up. The cohort was divided based on the chronic use of RAASi, as determined by pharmacy check-out data. The primary endpoint was defined as either the progression of ascending aortic diameter ≥ 4.5 cm or surgery for ascending aortic replacement. Results: The study included 262 patients with a mean age of 54.3±19.5 years, of whom 75.2% (n=197) were male, and 34.7% (n=44) had a diagnosis of hypertension. At baseline, the average size of the ascending aorta was 4.2±4.1 mm and 3.5±4.0 mm at the level of the aortic sinuses. The average follow-up time was 5.8±0.8 years. During follow-up, 23 patients underwent ascending aortic replacement with concurrent aortic valve replacement, 66 patients experienced progression of ascending aortic diameter ≥ 4.5 cm, and 2 patients died. Patients using RAASi (n=40) had a lower incidence of the primary endpoint compared to those without RAASi chronic therapy (12.8% vs. 24.8%, p=0.147). Multivariate analysis indicated that patients without RAASi chronic therapy had a significantly increased risk of the primary endpoint (HR=2.87, 95% CI [1.03-8.01], p=0.43). Conclusions: Our early findings suggest that RAASi may have a preventative role in the progression of BAV aortopathy.
Abstract 4124070: Dual-action Nanomatrix Coated Stent for Improving Endothelialization while Suppressing Restenosis and Inflammation
Authors: Ho-wook Jun, Robbie Cross, Xixi Zhang, Jun Chen, Yujin Ahn, Brigitta Brott, Peter Anderson, Jennifer Sherwood, Young-sup Yoon, Renu Virmani
Journal: Circulation (2024)

Introduction: The most common cause of cardiovascular disease (CVD) is atherosclerosis. The progression of atherosclerosis is characterized by endothelial cell dysfunction, proliferation of smooth muscle cell proliferation, and plaques which lead to progressive arterial stenosis. Bare metal stents (BMS) were developed to hinder stenosis, but re-stenosis has been observed following deployment. Drug-eluting stents (DES) have been developed to mitigate this, by releasing anti-proliferative drugs to suppress smooth muscle cell proliferation. However, these drugs also suppress endothelial growth. To address this, we are developing and evaluating a dual action nanomatrix coated stent comprised of a nitric oxide (NO) releasing peptide amphiphile (PA) and everolimus-encapsulated liposomes to improve endothelial proliferation and suppressing smooth muscle cell proliferation and inflammation. Materials and Methods: The nanomatrix coating contains a PA generated via solid phase peptide synthesis consisting of a nitric oxide donor and a cell adhesive ligand. The everolimus-encapsulated liposomes were prepared with DPPC, DOTAP, DSPE-PEG, and cholesterol via thin film rehydration, followed by encapsulation with everolimus. TEM was performed on liposomes to assess their stability. The release kinetics were evaluated via UV-vis of samples containing released everolimus. To evaluate the dual effect of the nanomatrix coating on metabolism, NO and everolimus were used to treat endothelial and smooth muscle cells, and an MTT assay was done. Results and Discussion: TEM showed that liposomes maintained stability over time. It was found that 60% of everolimus was released by day 30. The MTT assay showed that NO with everolimus increased endothelial cell metabolic activity and maintained or lowered smooth muscle cell activity compared to everolimus alone. Conclusions: Everolimus-encapsulated liposomes have potential as an effective delivery method of everolimus. NO and everolimus have a synergistic effect of improving endothelial function and suppressing smooth muscle cells.
Abstract 4123926: Suprasomatic Serial Growth of Right Heart Structures in Fetuses with Hypoplastic Left Heart Syndrome Demonstrated by Fetal Echocardiography
Authors: Sanghee Ro, Ian Milligan, Brian Schlosser, Michelle Gleason, Erik Michelfelder
Journal: Circulation (2024)

Background: In hypoplastic left heart syndrome (HLHS), the single right ventricle (RV) accounts for the entire cardiac stroke volume. This physiology may produce elevated transpulmonary flow velocities and dilation of the right heart structures. Little data exists regarding normal right heart dimensions and transpulmonary velocities in relation to somatic growth in these fetuses. We sought to assess serial changes in the size of right heart structures and pulmonary valve (PV) velocities in fetuses with HLHS and compare findings to fetuses with normal cardiac anatomy. Methods: A retrospective cohort study of fetuses with HLHS or normal cardiac anatomy confirmed by fetal echocardiogram between 1/1/13 – 12/31/22 was performed, excluding multiple gestation pregnancies. Fetal echocardiograms were assessed by an independent reviewer who obtained RV, PV and tricuspid valve annulus dimensions, and PV flow velocities. Nomograms were created for both HLHS and normal cohorts. The association between gestational age and PV velocity, PV annulus, RV diameter and tricuspid valve annulus was assessed and compared between groups using linear mixed models. Results: There were 290 total fetal echocardiograms for 177 patients with HLHS compared against 408 normal fetuses. [MG1] PV velocities were higher for patients with HLHS compared to normal cardiac anatomy throughout gestation (p &lt; 0.001). In addition, the PV velocity increased more rapidly with gestational age for the HLHS (+0.02 m/s/week) group compared to those with normal cardiac anatomy (+0.01 m/s/week) (p=0.019) (Figure 1). Similarly, the RV dimension grew more rapidly with gestational age for those with HLHS (+3.2% cm/week) compared to those with normal cardiac anatomy (+2.5% cm/week) (p&lt;0.001) (Figure 2). Lastly, the tricuspid valve annulus grew more rapidly with gestational age for patients with HLHS (+2.6% cm/week) compared to those with normal cardiac anatomy (+2.3% cm/week) (p=0.010) (Figure 3). While the PV annulus size increased with gestational age, there was not a significant difference in growth between the two groups (p=0.119). Conclusions: In fetuses with HLHS, the PV velocity, RV size and tricuspid valve size increase at a rate greater than normal somatic growth. These nomograms help identify expected RV size, tricuspid valve size and PV velocities for fetuses with HLHS and any who may deviate from the norm.
Abstract 4116148: Seasonal Variation of Unexpected Sudden Cardiac Death
Authors: Severi M Mattila, Hanna Latola, Lasse Pakanen, Jenni Hekkanen, Anette Eskuri, Juha Vahatalo, Olavi Ukkola, Juhani Junttila, Heikki Huikuri, Juha Perkiomaki
Journal: Circulation (2024)

Introduction: Data on the occurrence of unexpected sudden cardiac death (SCD) in different seasons are scanty and needs further exploration. Methods: Consecutive series of all unexpected SCD victims (n=5,869) who underwent medico-legal autopsy obligated by the Finnish law were prospectively collected from the geographically defined area in the Northern Finland during a twenty years period from 1998 to 2017. The seasonal variation of SCD and its possible causes were assessed in this large SCD victim cohort. Results: Unexpected SCD occurred more frequently during the first quarter of a year (from January to March) than during the other quarters (Figure 1). The occurrence of SCD during the twenty years follow-up was 4.5±0.24 during the first quarter of the year per month and 3.9±0.12 during the other quarters of the year per month on average (SCDs during the quarter of a year per month on average per 100,000 inhabitants per year, p&lt;0.001) (Figure 2). The weather was colder during the first quarter of the year (average temperature -9.1 degrees centigrade) than during the other quarters (average temperature +5.7 degrees centigrade). The snow cover was the largest during the first quarter of the year. Conclusion: Unexpected SCD occurred more commonly during the first quarter of a year (from January to March) than during the other quarters (from April to December). Cold weather, and perhaps winter-time physical activities in cold environment such as removal of snow, may have contributed to the increased occurrence of SCD during the first quarter of the year.
Abstract 4124226: Long-term exposure to air pollutants and incidence of cardiovascular disease events and mortality in The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air)
Authors: Michael T Young, R. Graham Barr, Alain Bertoni, Martha Daviglus, Ana Diez Roux, David Jacobs, Richard Kronmal, Ana Navas-Acien, Wendy Post, Lianne Sheppard, David Siscovick, Adam Szpiro, KAROL WATSON, Joel Kaufman
Journal: Circulation (2024)

Introduction: Exposure to ambient air pollution may increase the risk of cardiovascular disease events and mortality, but prior publications have primarily included administrative cohorts with outcomes that have not been individually reviewed and with air pollution estimates created without cohort-specific exposure monitoring. Multi-Ethnic Study of Atherosclerosis (MESA) is a multi-site cohort study designed specifically to prospectively collect and adjudicate cardiovascular disease (CVD) events. MESA Air recruited additional participants into sub-cohorts for enhanced air pollution variation and sample size. Research Question: The aim of this analysis was to characterize the relationship between long-term exposure to nitrogen dioxide (NO 2 ) and fine particulate matter (PM 2.5 ) and all-cause mortality and CVD events. Methods: Air pollution exposure was assessed using address history with a purpose-built exposure model incorporating cohort-specific monitoring including measurement and validation at participant homes. We used Cox models to assess the risk of rolling 2-year average exposures on all cause-mortality and on a composite CVD endpoint (definite angina, probable angina with revascularization, myocardial infarction, atherosclerosis or other CVD death, resuscitated cardiac arrest, and stroke). Models were stratified for baseline hazard by age, sub-cohort, and recruitment year and were additionally adjusted for age, sex, race/ethnicity, field center, smoking/second-hand smoke, pack-years, physical activity, education, income, neighborhood socioeconomic status, and statin use. Results: MESA Air participants were aged 44-87 years at enrollment between 2000 and 2007; follow-up averaged 14 years. 6,915 participants had follow-up for events, NO 2 exposure, and covariate information. We observed 1,442 deaths and 985 CVD events. The interquartile range over all 2-year averages was 10.5-23.1 ppb for NO 2 and 10.1-14.9 µ/m 3 for PM 2.5 . The adjusted hazard ratio (aHR) for a 10 ppb increment in NO 2 was 1.38 (95% CI: 1.17, 1.64) for all-cause mortality and 1.16 (95% CI: 0.95, 1.42) for incident CVD events. The aHR for a 5 µg/m 3 increment in PM 2.5 was 1.20 (95% CI: 0.99, 1.46) for all-cause mortality and 1.15 (95% CI: 0.95, 1.39) for incident CVD events Conclusions: These results add to growing literature demonstrating an association between air pollution exposure, mortality, and CVD in a cohort with well-characterized clinical endpoints and cohort-specific exposure assessment.
Abstract 4123530: Disparities in Hypertension Treatment Intensification among Adults in a Large United States Healthcare System
Authors: Aster Meche, Romsai Boonyasai, Yea-Jen Hsu, Raquel Greer, Hemalkumar Mehta, G Caleb Alexander, Jodi Segal, Lisa Cooper, John Jackson
Journal: Circulation (2024)

Background: There are racial/ethnic and socioeconomic status (SES) disparities in hypertension control, even in populations with regular care. It is unclear if clinical inertia by clinicians contributes to these disparities. Objectives: To quantify racial/ethnic and SES disparities in treatment intensification (TI) among adults with hypertension. Methods: We performed a retrospective cohort study using electronic health records from Johns Hopkins primary care practices from January 2018 to December 2022. We included non-Hispanic Black (Black) and non-Hispanic White (White) adults with at least 2 elevated blood pressure readings (&gt;=140/90 mm Hg) in the 12 months prior to the index primary care visit and a diagnosis of essential hypertension. We excluded patients with diagnoses of end-stage renal disease, liver disease, dementia, and metastatic solid tumor. Patients could contribute multiple index visits. We measured SES using the national Area Deprivation Index, which comprises 17 neighborhood-level SES indicators, and dichotomized the population into high and low median SES groups. We defined TI as a change in antihypertensive class or dose increase within 14 days of the index visit. We balanced covariates reflecting clinical need at the index visit (age, sex, blood pressure readings, cardiometabolic comorbidities, body mass index) and the index visit’s calendar time across racial/ethnic and SES groups using inverse probability weighting. We estimated annual race/ethnic and SES specific TI rates and risk difference measures of disparity with 95% confidence intervals (CI) using a clustered bootstrap. Results: The cohort included 25,287 patients (11,800 Black, 13,487 White) with 79,898 eligible visits. Black patients were more often younger, female, and residing in low SES areas compared to White patients. In 2018, TI rates for Black patients (37%, 95% CI: 36-38%) were slightly lower than rates for White patients (39%, 95% CI: 38-40%). In 2022, the disparity persisted, with the Black patients’ TI rate lower by 3% (95% CI: -5%, -1%). Similarly, low SES patients had lower TI rates than high SES patients by 2% to 3% over the study period. Conclusion: Black patients and those from low SES consistently had modestly lower rates of TI compared to White patients and those from high SES. It will be important to identify the drivers and clinical implications of these treatment disparities.
Abstract 4124277: Resorcimoline, a Novel Free Radical Scavenger, Exhibits Cardioprotective Effects Following Coronary Ischemia-reperfusion Injury
Authors: Kazuhiro Ueno, Joscha Mulorz, Kenshi Yoshimura, Kazuki Mori, Takayuki Kawashima, Haruto Nishida, Akihiro Higuchi, Osamu Tokumaru, Shinji Miyamoto
Journal: Circulation (2024)

Background: Ischemic heart disease remains the leading cause of death worldwide. Early coronary revascularization is the most important treatment. Recent findings have revealed that reactive oxygen species (ROS) can lead to tissue damage following coronary artery revascularization, known as ischemia-reperfusion injury. In this study, we focused on a novel free radical scavenger, resorcimoline (RML). Last year, we reported the scavenging activity of RML in vitro against multiple ROS, confirmed by the electron spin resonance spectrometry. Hypothesis: Resorcimoline might reduce ROS damage in cardiomyocytes, thereby exerting cardioprotective effects following coronary ischemia-reperfusion injury. Methods: Nine-to-eleven-week-old male Wistar rats were subjected to acute myocardial ischemia induced by ligation of the left anterior descending coronary artery for 30 minutes. Rats received intravenous injections of RML at 6 mg/kg before the ligation release or saline as a control. The heart sections were double-stained at 24-hour reperfusion with Evans blue and triphenyltetrazolium chloride to assess the infarct area. Cardiac function was evaluated at 2-day and 7-day reperfusion with echocardiography. Myocardial fibrosis was assessed at 7-day reperfusion by Masson’s trichrome staining. Primary cultured rat cardiomyocytes were treated with 10 μM angiotensin II for 3.5 hours and then exposed to RML for 30 minutes. Cellular ROS assay kits were used to assess the levels of ROS in the cardiomyocytes. Results: Infarct size in RML-treated animals was significantly smaller than in control animals (41.8±19.4% vs. 60.8±12.9%, p=0.03, Fig. 1A). Apoptotic cells in the border zone were significantly reduced in RML-treated animals (32.0±11.7% vs. 55.1±16.9%, p=0.01, Fig. 1B). Troponin I level in RML-treated animals was significantly lower than in control animals (p=0.04, Fig. 1C). Ejection fraction in RML-treated animals was significantly preserved at 2-day reperfusion and 7-day reperfusion when compared to control animals (p=0.001, p=0.003, Fig. 2A). Myocardial fibrosis area in RML-treated animals was significantly smaller than in control animals (23.9±11.7% vs. 40.6±15.6%, p=0.01, Fig. 2B). RML significantly reduced angiotensin II-induced ROS in cardiomyocytes in a concentration-dependent manner (Fig. 3A,B,C). Conclusion: Resorcimoline exhibits cardioprotective effects following coronary ischemia-reperfusion injury by reducing the infarct size and ROS damage in cardiomyocytes.