tbuckley/cabot-search huggingface dataset:
Abstract 4144036: Association of PM <sub>2.5</sub> Air Pollution with Inflammatory Biomarkers in Patients with Heart Failure
Authors: Benjamin Horne, Francois Haddad, Jeffrey Anderson, Holden Maecker, Tami Bair, Mary Johnson, Daniel Bride, Joseph Muhlestein, Juyong Kim, Stacey Knight, Kari Nadeau, Kirk Knowlton
Journal: Circulation (2024)

Background: Ambient fine particulate matter (PM 2.5 ) air pollution is associated with inflammatory conditions in the lungs, heart, and circulation. Inflammation may be causal in poor health outcomes, especially for people with existing disease. This study evaluated the association PM 2.5 levels with concentrations of 115 plasma inflammatory proteins. Methods: Patients with heart failure (HF) with preserved ejection fraction (HFpEF, n=44) and HF-free controls (n=35) from the Intermountain INSPIRE registry (NCT02450006) were tested for 115 targeted proteins (EMD Millipore and ELISA). HFpEF cases and controls were stratified by ambient PM 2.5 levels for low (PM 2.5 ≤7 µg/m 3 ) and higher exposure (PM 2.5 &gt;20 µg/m 3 ). PM 2.5 levels on the day of sample collection were evaluated, as well as 3-day and 7-day PM 2.5 moving averages (mAvg) of the concurrent day plus 2 or 6 immediately previous days. Samples drawn on days with PM 2.5 = 7.1-20.0 µg/m 3 were excluded. Results: Patients with HFpEF averaged 74.6±11.7 years of age (2.8 years since HF diagnosis) and 65.9% were female (controls: 72.0±8.7 years, 62.9% female). In HFpEF cases (Table), PM 2.5 &gt;20 µg/m 3 on the sample collection day was associated with higher IL-18 (p&lt;0.001 vs. ≤7 µg/m 3 ) and C-C motif chemokine ligand 27 [CCL27, also known as cutaneous T cell-attracting chemokine (CTACK)] (p&lt;0.001 vs. ≤7 µg/m 3 ), with a trend for TNF-α (p=0.012). The 3-day PM 2.5 mAvg was significant for IL-18 and CCL27, while CCL27 remained significant for the 7-day mAvg (Table). In controls, none of the 115 biomarkers differed based on PM 2.5 levels. Age did not differ in cases or controls by PM 2.5 category. Conclusions: In a pilot study evaluating the inflammatory response to air pollution, CCL27 and IL-18 were higher in patients with HFpEF during short-term PM 2.5 elevations. Inflammatory biomarkers were not different based on PM 2.5 levels in people free of HF. Short-term PM 2.5 elevations may induce inflammation and these findings suggest that people with HFpEF struggle to restore homeostasis.
Abstract 4144061: BubR1 Insufficiency Recapitulates Changes Associated with Age-Related Cardiac Pathologies
Authors: Renju Pun, Aradhana Thapa, Sylar Takafuji, Gabrielle Kay, Rexton Suzuki, Aliya Haas, Michael Kim, Brian North
Journal: Circulation (2024)

Cardiovascular diseases (CVDs) continue to be the leading cause of mortality worldwide, surpassing all other conditions in annual fatalities. Aging is a significant risk factor for CVDs, as it induces structural and functional alterations in the cardiovascular system. BubR1, a serine/threonine protein kinase, plays a crucial role in regulating the spindle assembly checkpoint during mitosis. Previous studies have shown that BubR1 insufficiency results in premature aging phenotypes, including kyphosis, cataracts, and reduced lifespan. BubR1 hypomorphic mice, which express approximately 10% of normal BubR1 protein levels, display conduction abnormalities such as a prolonged QTc interval, and suffer from sudden cardiac death. Given that BubR1 protein levels decline with age, we hypothesize that BubR1 is essential for maintaining adult cardiac structure and function, and its loss may drive age-related cardiac pathophysiology. In this study, we characterized the tissue, cellular, and molecular phenotypes present in hearts isolated from BubR1 hypomorphic mice. Structural analysis revealed that these mice exhibit cardiac hypertrophy, as shown by increased heart weight and ventricular cardiomyocyte size. Masson’s trichrome staining indicated elevated fibrosis in both the ventricular and perivascular regions of BubR1 hypomorphic hearts. At the molecular level, these hearts showed increased levels of p21 and phospho-γH2AX, markers of cellular senescence and DNA damage. Transcriptomic profiling further indicated that BubR1 insufficiency leads to dysregulation of pathways critical to cardiac function, including those related to voltage-gated ion channel activity, contractile fiber organization, and extracellular matrix organization. A comparative analysis between BubR1 hypomorphic hearts and aged hearts revealed a set of common dysregulated genes, suggesting shared mechanisms underlying BubR1 insufficiency and cardiac aging. Since the risk of heart failure increases with age, we conducted additional comparison between BubR1 hypomorphic mice and end-stage heart failure patients which suggested that BubR1 insufficiency mimics the transcriptomic changes associated with heart failure, such as increased expression of Nppa and Nppb genes. Overall, our findings suggest that BubR1 is a key regulator of age-related cardiac pathologies and represents a potential therapeutic target for CVDs.
Abstract 4144188: A Meta-Analysis of Prospective Studies Comparing Short and Longterm Outcomes of Trans-Catheter Aortic Valve Replacement in Patient with and without Cancer
Authors: Muhammad Aslam Khan, Nouman Shafique, Hammad Rahman, Asna Aafreen, Anza Muhammad, Hitesh Bhatia, Abid Nawaz Khan Khan, Usman Akbar, Alamzaib Khan, Adnan Haider, Taimoor Haider, Shraddha Bhattarai, Bilal Khan, Bikal Lamichhane
Journal: Circulation (2024)

Objectives: Trans-catheter Aortic Valve Replacement (TAVR) is the preferred treatment of choice for improving clinical outcomes in patients with Severe Aortic Stenosis. Studies published in the past in patients undergoing TAVR with cancer have shown a lower risk of short-term mortality but an increased risk of long-term mortality. This study aims to compare short-term (within 30 days) and long-term (3 years) outcomes in patients with and without a diagnosis of cancer. Methods: Electronic databases like MEDLINE, PUBMED, and COCHRANE library were thoroughly searched from the date of inception till May2024. 4 observational prospective studies were included in this meta-analysis. Outcomes of interest included short-term mortality (&lt;30-day), stroke, pacemaker insertion, vascular complications, major bleeding events and long-term mortality (&gt;3 year). The results were reported as Risk Ratio (RR) with 95% confidence intervals (CI), using a random effects model. Results: This meta-analysis included 6603 patients from 4 studies. Among those undergoing TAVR, individuals with cancer showed clinically significant reduction in short-term mortality (RR 0.63, 95% CI: 0.43-0.94, p = 0.02) but had higher rate of long-term mortality (RR 1.27, 95% CI: 1.15-1.42, p = 0.00001) compared to those without cancer. Additionally, more major bleeding episodes (RR of 1.17, 95% CI: 1.06- 1.29, p: 0.001) were observed in the cancer group compared to the non-cancer population. No significant difference was noted between the two groups regarding risk of Stroke (RR of 0.98, 95% CI: 0.67- 1.43, p: 0.91), pacemaker (PPM) insertion (RR 1.09, 95% CI: 0.96-1.24, p: 0.20), and Vascular site complications (RR 1.09, 95% CI: 0.95- 1.25, p: 0.20). Conclusion: Our study shows that cancer patients undergoing TAVR have good short-term mortality rates and comparable perioperative outcomes, but higher long-term mortality as compared to those without cancer. More randomized controlled trials are needed to further assess the long-term outcomes in this population.
Abstract 4144239: The Relationship Between Endothelial Function and Tissue Characterization After Drug-coated Balloon for De-novo Coronary Lesion
Authors: Tsutomu Kawai, Mitsutoshi Asai, Takashi Morita, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondo, Masahiro Seo, Jun Nakamura, Takeshi Fujita, Takahisa Yamada, Masatake Fukunami
Journal: Circulation (2024)

Background: The previous our study showed that vasomotion may be better preserved after drug-coated balloon (DCB) treatment than after stenting. However, there is no information available on the relationship between endothelial function and tissue characterization after DCB treatment. Aims: The purpose of this study was to investigate the relationship between endothelial function and tissue characterization after DCB for de-novo coronary lesion. Methods: We prospectively studied 19 patients who underwent acetylcholine provocation test and intravascular imaging at 8-month after DCB treatment. To evaluate endothelial-dependent vasomotion, the mean lumen diameter of the distal segment, beginning 5 mm and ending 15 mm distal to the edge of the treated segment, was quantitatively measured by angiography during the acetylcholine provocation test. Tissue characterization was assessed with integrated backscatter intravascular ultrasound (IB-IVUS). Results: There was a positive correlation between endothelial-dependent vasomotion and the proportion of lipid plaque in treated segments (r 2 =0.610, p=0.009). On the other hand, there were negative correlations between endothelial-dependent vasomotion and the proportion of dense fibrous or calcified plaque in treated segments (r 2 =-0.709, p=0.001, r 2 =-0.773, p&lt;0.001). Conclusion: Endothelial-dependent vasomotion was better preserved in lipid-rich lesions than in dense fibrous or calcified lesions, suggesting that endothelial function could be more impaired in lesions with advanced atherosclerosis after DCB treatment.
Abstract 4144055: Adverse Physical Environment, Housing, and Economic Conditions: Their Impact on Maternal Cardiovascular Health during and Post-Pregnancy
Authors: Toluwalase Awoyemi, Anderson Anuforo, Oluwaremilekun Tolu-Akinnawo
Journal: Circulation (2024)

Background: Maternal cardiovascular health is a critical concern, particularly during and following pregnancy. Previous studies have highlighted the influence of social determinants on health outcomes, but the specific impact of adverse Physical Environment, Housing, and Economic Conditions on maternal cardiovascular health remains underexplored. Methods: Using the TriNetX global health research network within the US Collaborative Network, we explored how adverse Physical Environment, Housing, and Economic Conditions (ICD10CM: Z58 and ICD10CM: Z59) impact maternal cardiovascular health during pregnancy and within one year postpartum. Using, propensity score matching (PSM) analysis, our study compared two cohorts: women aged 15 to 60 who experienced issues related to Physical Environment, Housing, and Economic Conditions during or after pregnancy from 2008 to 2023, and women in the same age range who did not face such issues, thus representing a favorable physical environment, housing, and economic conditions. Results: Challenges related to the physical environment, housing, and economic conditions significantly increased the risk of all-cause mortality (OR: 3.237, 95% CI: 2.064 to 5.075, p&lt;0.001), acute myocardial infarction (MI) (OR: 2.831, 95% CI: 1.422 to 5.634, p=0.002), major adverse cardiac and cerebrovascular events (MACCE) (OR: 2.734, 95% CI: 1.953 to 3.782, p&lt;0.001), and ischemic stroke (OR: 2.082, 95% CI: 1.074 to 4.037, p=0.026). On the other hand, no significant correlation was found between adverse physical environment, housing, and economic conditions and the incidence of peripartum or postpartum preeclampsia (OR: 0.994, 95% CI: 0.904 to 1.093, p=NS), peripartum or postpartum eclampsia (OR: 1.178, 95% CI: 0.852 to 1.629, p=NS), hemorrhagic stroke (OR: 1.202, 95% CI: 0.519 to 2.782, p=NS), or peripartum cardiomyopathy (OR: 0.977, 95% CI: 0.631 to 1.511, p=NS). Conclusion: Women exposed to adverse physical environment, housing, and economic conditions conditions experienced higher rates of cardiovascular problems compared to those in more favorable circumstances.
Abstract 4144252: Associations of Dietary Zinc Intake with Cardiovascular Disease and Mortality: Results from the Prospective Urban and Rural Epidemiology (PURE-China) Study
Authors: Xiaocong Li, Qiujing Cai, Yilin Huang, Biyan Wang, Wei Li
Journal: Circulation (2024)

Background: Zinc is an essential trace element that can affect cardiovascular health through a variety of pathways including influencing vascular endothelial cell stability and signaling processes. Dietary intake is the main source of zinc in humans. Epidemiologic studies on the association between dietary zinc and cardiovascular disease remain scarce, especially in China. Aims: To investigate the associations of dietary zinc intake with the risk of cardiovascular disease and mortality in Chinese adults. Methods: Based on the Prospective Urban and Rural Epidemiology in China (PURE-China) study, we included people aged 35-70 years from 12 provinces in China. The daily dietary intake was recorded by a semi-quantitative food frequency questionnaire designed for Chinese people, and the daily dietary zinc intake was obtained based on the nutrient content of each food provided in the Chinese Food Composition Table (2002). Cox frailty proportional hazards models were developed to evaluate the association between dietary zinc intake with mortality and major cardiovascular diseases. Results: A total of 41 310 participants were included in the study after excluding participants with incomplete information, cardiovascular disease at baseline, and no follow-up information. The mean dietary zinc intake was 14.07±6.10 mg/d and the median level was 12.98mg/d. After 11.9 years of follow-up, 3 209 (7.8%) developed new cardiovascular diseases, 5.3% (2 170) died during follow-up, 714 (1.7%) died from cardiovascular diseases and 4 594 (11.1%) had a composite endpoint event. Compared with those in the second quartile of dietary zinc intake, those in the fourth quartile had a higher risk of all-cause mortality (HR[95%CI]: 1.20 [1.01-1.44]), stroke (HR[95%CI]: 1.25 [1.05-1.48)), and composite outcomes (HR[95%CI]:1.17 [1.03-1.32]). Those in the fourth quartile had a higher risk of major cardiovascular disease (HR[95% CI]:1.17 [1.03-1.32]) compared with those in the first quartile of dietary zinc intake. Conclusions: Excessive dietary zinc intake in the Chinese population may be associated with an elevated risk of cardiovascular disease and death. Further studies should be conducted to clarify the upper limit of dietary zinc intake.
Abstract 4144093: Stent-Based Sensor System for Wirelessly Monitoring Arterial Stiffness and Restenosis
Authors: Robert Herbert
Journal: Circulation (2024)

Introduction: Implantable vascular electronics offer opportunities to improve patient monitoring and treatments. However, device manufacturability, alongside strict requirements of size, mechanics, and sensing capability, have hindered the development of implantable vascular sensors. Although stents are commonly used with over 3 million stents implanted in cardiovascular arteries every year, there have been minimal efforts to integrate sensing functionality with stents. A promising target for a stent-based electronic system is to monitor the progression of restenosis. Towards this, we report a stent-based sensor system utilizing an electronic stent and a soft sensor to wirelessly measure changes in arterial stiffness and monitor restenosis. Methods: A multi-step, rotational laser micromachining was developed to form an electronic stent with layers of stainless steel, polymer, gold, and parylene. Soft, capacitive sensors were printed with elastomer, polymer, and silver nanoparticles. Integrating a stent and sensor forms a passive, wireless sensor. An external loop antenna interrogates the implantable device to record a resonant frequency dependent on arterial strain. The device is evaluated in vitro with silicone models and ex vivo in an ovine coronary artery. Results: Figure 1a illustrates the device while the sensor and stent components are highlighted in Figures 1b and 1c. Capacitive strain sensor design was studied to achieve a gauge factor over 3 and the ability to measure strain changes as small as 0.15%. Stent design and fabrication strategies were developed to yield a stent that replicates conventional stent mechanics while offering wireless connectivity to an external antenna. Figure 1d shows the system before and after expansion with a balloon catheter. Once expanded, the device is operated via inductive coupling to wirelessly record changes in resonant frequency and measure changes in arterial strain or artery diameter (Figure 1e). Restenosis levels of 0% up to 90% were tested by thickening the artery wall along the length of the stent and are summarized in Figure 1f. Figure 1g shows the sensor implanted in the coronary artery of an ovine heart for ex vivo testing. Conclusions: We have demonstrated a vascular electronics system for the monitoring of arterial stiffness and restenosis. Collectively, our studies of vascular device fabrication and sensor design provide strategies to create vascular electronics for enhanced patient and disease monitoring.
Abstract 4144136: Assessing the Efficacy and Safety of Olezarsen in Lowering Triglyceride Levels: A Systematic Review and Meta-Analysis
Authors: Zoha Shahzad, Osama Ijaz, Asad Gul Rao, Warda Rasool, Shariq Ahmad Wani, Faateh Rauf, Badr ilmaguook, Arslan Ahmed Khan, Ali Hanif Bhatti, Asma Batool
Journal: Circulation (2024)

Background: Elevated fasting serum triglyceride (TG) levels are linked to an increased risk of cardiovascular disease. Olezarsen is an inhibitor of apolipoprotein C3 (apo-C3) production with a potential to decrease TG levels and thereby, reduce the risk of cardiovascular disease. Research Question: Is olezarsen efficacious and safe in reducing the TG levels? Aim: This meta-analysis aims to evaluate the efficacy and safety of olezarsen in patients with hypertriglyceridemia. Methods: A literature search was carried out on Medline, Embase, Google Scholar, Cochrane CENTRAL, Scopus, and clinicaltrials.gov. Only randomized controlled trials (RCTs), including adult patients with hypertriglyceridemia and treated with olezarsen, were included. The primary outcome assessed was the mean change in the level of TG, whereas the secondary outcomes were changes in the apo-C3, apo-B48, and non-HDL cholesterol levels at the end of the 6-month follow-up period. Various adverse events were also assessed. Review Manager 5.4 was used to calculate standardized mean differences (SMD) with 95% confidence intervals (95% CIs) using a random effects model. Results: Three RCTs involving 334 patients in total, with 248 receiving olezarsen and 86 receiving placebo, were included. The analysis revealed that at the end of the follow up period, there was a significant change in the levels of TG (SMD -52.04, 95%CI: -64.55 to -39.52; p&lt;0.00001; I 2 =72%), apo-C3 (SMD -69.84, 95%CI: -76.82 to -62.86; p&lt;0.00001; I 2 =33%), apo-B48 (SMD -14.50, 95%CI: -21.29 to -7.71; p&lt;0.00001; I 2 =8%) and non-HDL cholesterol (SMD -21.54, 95%CI: -27.96 to -15.12; p&lt;0.00001; I 2 =0%). Olezarsen was not associated with any adverse event as demonstrated by the pooled analysis of adverse events. Meta-regression showed that no outcomes were significantly associated with age and BMI as covariates. Conclusion: A significant reduction was noted in TG, apoC-III, apo-B48, and non-HDLC levels, indicating a significant effect of olezarsen on these parameters. Additionally, olezarsen exhibited no significant side effects, making this medication comparatively safe. More research may be warranted to validate these findings and explore the drug's impact on cardiovascular outcomes.
Abstract 4144106: Markers of Abdominal Aortic Stenoses in Williams Syndrome
Authors: Elisa McCarthy, Michelle Kaplinski, Gregory Adamson, Kirstie MacMillen, Evan Zucker, Abanti Chaudhuri, Claudia Algaze, Ronnie Collins
Journal: Circulation (2024)

Background: Renal artery stenosis (RAS) is common in Williams syndrome (WS). Gold standard advanced cardiovascular (CV) imaging (aCVI) required to confirm RAS (CT, catheter angiography, or MRI) often requires anesthesia, which is associated with sudden CV events in WS. We sought to identify echocardiographic CV measures associated with abdominal arteriopathy in WS that might be used to determine which patients require aCVI. Methods: We retrospectively reviewed all patients with WS treated at our center with aCVI from 2015 to 2022. From aCVI obtained, we measured the diameter of the abdominal aorta (Ao) at the hiatus (AoH), right renal artery (AoRRA), and celiac trunk (AoCA), and the origin, proximal aspect (4mm from the origin), and midpoint of the RRA, left renal artery (LLA), celiac artery (CA), superior mesenteric (SMA) and inferior mesenteric (IMA) arteries. For all aortic measurements, we calculated Z-scores using published formulae (Hegde, 2015). To our knowledge, there are no Z-scores available for pediatric SMA, IMA, or renal arteries, so we used a ratio reflecting the most severe area of narrowing (either origin:midpoint or proximal:midpoint). From the echo closest in absolute time to aCVI, we measured the ascending Ao wall thickness in the suprasternal sagittal echocardiographic view and compared it to the same measurement in age- and height-matched controls. Results: There were 48 patients with WS and aCVI included in the study (26 CT, 17 cath, 5 MRI). In 44 (92%), the abdominal Ao was diffusely stenotic (Z-scores &lt;-2 at AoH, AoCA, or AoRRA). There was strong correlation between AoH and AoCA (r 2 =0.76), AoH and AoRRA (r 2 =0.79), and AoCA and AoRRA (r 2 =0.69) (all Z-score comparisons). There was moderate correlation between AoH Z-score and worst narrowing ratio of CA (r 2 =0.40), and between the worst narrowing ratios of the RRA and LRA (r 2 =0.53). Ascending Ao from 47 patients with WS (obtained at a median 44 days from aCVI) was thicker in WS compared to 47 controls (22 vs 17mm, p&lt;0.001), but did not correlate with any abdominal arterial measures. Conclusion: Though often a marker of severe cardiac disease in WS, ascending Ao thickness does not predict abdominal arterial stenoses in WS. However, stenosis of AoH on aCVI is correlated with other abdominal stenoses in WS. Since AoH can be measured by echo, more work is necessary to determine whether this could serve in WS as an indicator of further abdominal stenoses and need for subsequent aCVI.