tbuckley/cabot-search huggingface dataset:
Abstract 4139549: Air Filtration-Associated Changes in Cardiometabolic Protein Markers: Exploratory Analysis within a Randomized Controlled Trial
Authors: Clarine Long, Maria Florencia Schlamp, Terry Gordon, Lorna Thorpe, Jonathan Newman, Sharine Wittkopp
Journal: Circulation (2024)

Background: Fine particulate matter air pollution (PM 2.5 ) exposure is linked with increased risk of cardiovascular disease (CVD) events, increases in blood pressure and inflammation. By decreasing PM 2.5 concentrations, portable air cleaners (PACs) reduce PM 2.5 exposure and may mitigate inflammatory responses to exposure. We hypothesized that PAC use is associated with changes in serum concentrations of protein biomarkers associated with CVD risk. Aim: We aimed to quantify changes in protein biomarkers after 4 weeks of PAC use to provide insights into the proteomic response to reduced PM 2.5 . Methods: We performed a randomized, double-blind, sham-controlled trial of PACs in 44 outpatient adults with stable HTN and no known CVD. Participants were randomly assigned to either the true PAC group or the sham PAC (placebo) group. Serum concentrations of 369 protein biomarkers associated with CVD risk were measured using the Olink Cardiometabolic Explore I panel before and after 4 weeks of PAC use. The associations between PAC use and changes in protein concentrations were analyzed using linear mixed-effects models, adjusting for age, sex and BMI. Results: Median (IQR) age of participants was 57.5 (51-68) years, 29 (66%) were female, and 21 (48%) had BMI &gt; 30. The changes in expression of 7 protein biomarkers after air filtration differed significantly comparing true versus sham: SSC5D, F7, GH1, LEPR, TFPI, COL4A1, THPO (all p-values &lt; 0.05 for interaction term). SSC5D and THPO were downregulated while the remainder were upregulated. PAC use may have beneficial effects on pathways associated with blood coagulation (increased F7 and TFPI, decreased THPO) and healing (increased LEPR, COL4A1, GH1) and innate immune response (decreased SSC5D). Though most of these have not been directly studied in relation to PM 2.5 , F7 has been shown to decrease with increased air pollution, concordant with our results. Conclusions: We showed significant effects of air filtration on serum concentrations of seven protein biomarkers linked with CVD. These results provide insight into potential mechanisms by which PAC use may reduce CVD risk.
Abstract 4139840: Impact of Sodium-Glucose Cotransporter 2 Inhibitors on Acute Kidney Injury Post Coronary Artery Bypass Grafting ：A Retrospective Cohort Study and Meta-Analysis
Authors: Xiaozheng Zhou, Xiubin Yang, Kun Hua
Journal: Circulation (2024)

Background: sodium-glucose cotransporter 2 inhibitors (SGLT2i) , a new type of oral hypoglycemics agent used to treat type 2 diabetes, have a positive effect on the progression of heart failure, but there is a concern with the association between SGLT2i and acute kidney injury (AKI). Materials and Methods: We retrospectively evaluated consecutive patients undergoing CABG surgery from January 2018 to December 2021 in the hospital. A cohort of patients who had been prescribed SGLT2i was identified and matched by propensity score with a cohort of patients who had not been prescribed SGLT2i in a ratio of 1:3. The primary outcome was AKI following CABG. Furthermore, a meta-analysis was conducted on the relationship between SGLT2i and acute kidney injury (AKI). Four studies, comprising a total of 25,116 patients, were included in the analysis. Results: A total of 403 patients who had received SGLT2i and 1209 without SGLT2i were included in the analysis. AKI was observed in 54 patients (13.4%) in the SGLT2i group and 373 patients (30.9%) in the non-SGLT2i group following CABG. The SGLT2i exhibited a lower incidence of AKI compared with the non-SGLT2i (P &lt; 0.001). The findings of the meta-analysis indicated that SGLT2i was associated with a decreased incidence of AKI (P &lt; 0.001; OR= 0.525, [95% CI, (0.437-0.631]). Conclusion: The results of our prospective study indicated a reduced risk of AKI in patients undergoing CABG and were treated with SGLT2i.
Abstract 4139776: Correlation of Skin Sympathetic Nerve Activity (SKNA) with Renal Sympathetic Nerve Activity (RSNA) in Rats: A Novel Non-Invasive Indicator of Sympathetic Activity
Authors: Ryosuke Nakashima, Keisuke Shinohara, Shota Ikeda, Sho Matsumoto, Daisuke Yoshida, Yoshiyasu Ono, Hiroka Nakashima, Ryohei Miyamoto, Kohtaro Abe
Journal: Circulation (2024)

Introduction: The sympathetic nervous system plays a crucial role in cardiovascular regulation and in the pathophysiology of cardiovascular diseases such as hypertension, arrhythmias, and heart failure. Therefore, assessment of sympathetic nerve activity is important for understanding the pathophysiology in patients with cardiovascular disease. In humans, the gold standard for indicators of sympathetic nerve activity is muscle sympathetic nerve activity recording, but this is invasive and not a versatile method because it requires special techniques and equipment. Recently, skin sympathetic nerve activity (SKNA) has been reported as a novel indicator of cardiac sympathetic nerve activity derived from non-invasive ECG recording in humans. However, the utility and validation of SKNA have not been fully established. Research Question: Does SKNA truly reflect sympathetic nerve activity? Aims: To evaluate whether SKNA correlates with renal sympathetic nerve activity (RSNA), an established measure of sympathetic activity, in experimental animals. Methods and Results: Blood pressure, heart rate, RSNA, and SKNA were measured simultaneously in Sprague-Dawley rats under anesthesia. RSNA was recorded directly using bipolar electrodes, and SKNA was isolated from body surface ECG recordings by band-pass filtering to remove electrocardiograms and electromyograms. Changes in RSNA and SKNA were evaluated when blood pressure was altered by intravenous phenylephrine or nitroprusside and when the sympathetic nervous system was blocked by intravenous hexamethonium, a ganglion blocker. Baroreceptor reflexes functioned; RSNA decreased when blood pressure was raised with phenylephrine and increased when blood pressure was lowered with nitroprusside. SKNA was altered similarly to these RSNA responses (Figure A). In addition, administration of the ganglion blocker hexamethonium markedly attenuated RSNA, and SKNA was attenuated similarly to RSNA. Changes in SKNA in response to phenylephrine or nitroprusside were significantly correlated with changes in RSNA (r 2 =0.54, p &lt;0.05; Figure B). Conclusion: SKNA correlates with RSNA, an established measure of sympathetic activity, in rats. Our study confirms that SKNA can be an alternative, novel indicator of sympathetic activity. This non-invasive SKNA recording will allow for application to animal experiments under unanesthetized awake conditions.
Abstract 4140224: Conservative management of patent ductus arteriosus in preterm infants: a systematic review and meta-analysis of randomized controlled trials
Authors: Maryam Asif, Rajanikant Kumar, Efeoghene Praise Epia, Mark Abdelnour, Joo Young Belen Kim Kim, Anne Boakyewaa Anokye-Kumatia, Vrunda Kulkarni, Rimmo Loyi Lego, Syed Ali Farhan Abbas Rizvi, Huzaifa Ahmad Cheema, Adeel Ahmad, Wajeeh Rehman, Raheel Ahmed, Sourbha Dani
Journal: Circulation (2024)

Background: In recent years, there has been a rise in the adoption of conservative approaches to managing patent ductus arteriosus (PDA) in preterm infants. Systematic appraisal of the clinical evidence supporting this approach is essential for guiding recommendations in clinical guidelines. Methods: A comprehensive search of MEDLINE (PubMed), Embase, the Cochrane Library, and ClinicalTrials.gov, spanning from inception to April 2024, was conducted to identify all relevant randomized controlled trials (RCTs) that evaluated conservative management of patent ductus arteriosus (PDA) in preterm infants. Conservative management was defined as approximately ≤25% open-label pharmacological treatment with ibuprofen, indomethacin, or paracetamol and/or ligation/endovascular closure. Our primary outcomes were the risk of all-cause mortality and bronchopulmonary dysplasia. We used RevMan 5.4 to pool risk ratios (RRs) under a random-effects model, ensuring a rigorous and reliable analysis. Results: Our review included 6 RCTs. There was no difference in the risk of mortality (RR 0.83; 95% CI: 0.64-1.08, I 2 = 0%) and BPD (RR 0.89; 95% CI: 0.76-1.03, I 2 = 22%) between the conservative management and active treatment groups. The rates of necrotizing enterocolitis, intraventricular hemorrhage, retinopathy of prematurity, sepsis, pulmonary hemorrhage, and the need for surgical ligation or transcatheter occlusion were similar between the two groups. Conclusions: The meta-analysis showed no difference in the risk of all-cause mortality, BPD, or other clinical outcomes between a strategy of conservative management compared to active treatment. These findings support a conservative approach for the management of PDA in preterm infants. Future studies should focus on cost-effectiveness analyses between the two approaches and investigate important subgroups, such as extremely preterm births.
Abstract 4139955: Electronic Frailty Index as a Predictor of Clinical Outcomes in Older Adults with Myocardial Infarction
Authors: Zachary Pruitt, Chuka Ononye, Allison Kleinsmith, Sean Doherty, karl richardson
Journal: Circulation (2024)

Background: Myocardial infarction (MI) is a leading cause of mortality worldwide, and adverse outcomes among hospitalized patients are notable, particularly among older patients who experience frailty. Frailty is characterized by poor physiologic reserve and often results in poor response to medical insults. This study aims to assess the utility of a health record-based Electronic Frailty Index (eFI) in predicting clinical outcomes among these patients. Methods: This study is a single-center, retrospective cohort study of 390 patients aged 65 and older admitted with MI from October 2017 to January 2021. Data was collected using the ACC Chest Pain-MI registry and the electronic health record. Patients were divided into two cohorts: Fit (eFI &lt;0.1) and Not Fit (eFI ≥0.1). Data was analyzed using descriptive statistics and multivariate nominal logistic regression. The primary outcome was in-hospital mortality. Secondary outcomes included revascularization strategy, Major Adverse Cardiac Events (MACE), adverse bleeding, development of cardiogenic shock, need for mechanical circulatory support, hospital length of stay, and discharge destination. Results: The mean age and standard deviation (SD) of the study cohort was 75 ± 6.97 years, with 130 (33%) females, 334 (86%) Caucasians, and 292 (75%) designated as Not Fit. Not Fit patients had a higher frequency of comorbid disease than Fit patients (Table 1). In-hospital mortality was significantly greater among Not Fit patients (8 vs. 2%, p = 0.03). Not-fit patients were more likely to be discharged to a hospice facility (6 vs. 1%, p = 0.05). Fit patients were more likely to undergo surgical revascularization (28 vs. 17%, p = 0.02). Additional secondary outcomes did not differ significantly between groups. A multivariate nominal logistic regression found that the patient’s Fit status (p = 0.03) and age (p = 0.05) were significant drivers of in-hospital mortality. Conclusion: Among patients admitted with MI, Not Fit patients had a greater likelihood of in-hospital mortality. Age and Fit status drove this association significantly, suggesting that lower physiologic reserve may lead to poorer clinical outcomes. Further study is needed to better characterize eFI as a risk-stratification tool for older patients with MI.
Abstract 4139932: Glucagon-like peptide-1 Receptor Agonists reduce the Incidence of Echocardiographic Pulmonary Hypertension
Authors: Jonah Garry, Suman Kundu, Svetlana Eden, Charles Alcorn, Matthew Freiberg, Evan Brittain
Journal: Circulation (2024)

Introduction: No interventions decrease the risk of developing pulmonary hypertension (PH). We hypothesize Glucagon-like peptide-1 receptor agonists (GLP-1) reduce risk of PH through salutary changes in metabolism, weight, and the pulmonary vasculature. We examined GLP-1 exposure and development of PH among pts with diabetes (DM) in a national healthcare system. Methods: Pulmonary artery systolic pressure (PASP) estimates were extracted from TTEs in the Veterans Affairs system. PH (primary outcome) was defined as PASP &gt;35 mmHg. Individuals free of PH on or after 1/2007 (baseline) were followed through the development of PH, death, or censored on 12/2020. The primary exposure was GLP-1 prescription modeled as: 1) Baseline exposure 2) Time-updated exposure and 3) Cumulative days of exposure (among exposed). We used multivariable cox models adjusted for demographics, comorbidities, and clinical characteristics in Table 1 . Results: We identified 147,619 patients with DM (63 years [IQR 59-67], 95% Male, 21% Black) with a baseline TTE free of PH. Median follow up was 4.5 years (2.3-7.3 IQR). Of these, 2,621 pts were exposed to GLP-1 at baseline and 5,699 pts after baseline. Median time on drug (among exposed) was 296 days (120-570 IQR). Characteristics of exposed vs unexposed at baseline are displayed in Table 1 with Age-adjusted Kaplan Meier curve in Figure 1A . GLP-1 exposure associated with decreased risk of incident PH when modeled as baseline exposure (HR 0.76; 95% CI 0.67-0.87), time-varying exposure (HR 0.82; 95% CI 0.76-0.89), and time-varying exposure restricted to pts without baseline exposure (HR 0.85; 95% CI 0.78-0.94). Risk of PH decreased as days on GLP-1 increased ( Figure 1B ). At 90 days on drug, we observed decreased risk of PH (HR 0.94; 95%CI 0.92-0.96). Conclusions: GLP-1 exposure at baseline or de novo during follow up is associated with decreased incidence of PH in pts with DM. The benefit from GLP-1 starts near 90 days and increases with time on drug.
Abstract 4139964: Evolving Baseline Risk in Patients With Transthyretin Amyloid Cardiomyopathy: A Systematic Literature Review of Clinical Trials
Authors: Ahmad Masri, Richard Wright, Marissa Betts, Louis Lavoie, Aiswarya Shree, Liana Hennum, Jean-Francois Tamby, Heather Falvey, Sandesh Dev, Jose Nativi-Nicolau
Journal: Circulation (2024)

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is estimated to occur in 120,000 US adults and remains underdiagnosed. However, awareness of ATTR-CM has improved following the introduction of new diagnostic tools and disease-modifying treatments. Hence, patients (pts) enrolled in contemporary clinical trials could be at an earlier stage of the disease than pts in past clinical studies. Aim: To assess temporal trends in the baseline risk of pts with ATTR-CM enrolled in clinical trials. Methods: Embase, MEDLINE, CENTRAL, and conference websites were searched on November 23, 2023, for peer-reviewed articles and abstracts. Randomized and single-arm clinical trials examining treatments for ATTR-CM were included, and baseline characteristics and outcomes in pts treated with placebo (PBO) were compared across studies. Results: We reviewed 39 publications derived from 4 randomized and 4 single-arm trials. Studies enrolled pts between 2008 and 2021, although 1 study (INOCARD, 2022) did not report years of enrollment. Several baseline characteristics were comparable across studies, including sex, age, race/ethnicity, genotype, and troponin I level. NYHA class at baseline varied with year of enrollment, with fewer NYHA class III pts in recent trials (Figure). Recent trials also showed a trend toward lower NT-proBNP levels (medians ranging from 1911-3178 pg/mL) and higher eGFR levels (means ranging from 54.7-69.0 mL/min/1.73 m 2 ). In PBO groups, all-cause mortality (ACM) rates at 12 months dropped from 9% in ATTR-ACT (enrolled 2013-2015) to 6.9% in ATTRibute-CM (enrolled 2019-2020) and 5.6% in APOLLO-B (enrolled 2019-2021); ACM rates at 30 months dropped from 42.9% in ATTR-ACT to 25.7% in ATTRibute-CM. Conclusions: This systematic review found that disease-modifying treatments and diagnostic advances have led to earlier diagnosis of pts with ATTR-CM. Recent clinical trials appear to have enrolled pts with a better prognosis. Comparisons of results across these trials are limited and should acknowledge the potential impact of variability in baseline risks among trial populations.
Abstract 4139646: Disparities in Palliative Care Utilization Among Patients With Heart Failure and LVAD implantation: A Nationwide Comparative Analysis
Authors: Enad Haddad, Sudeep Nugooru, Shreeja Shah, Prerana Sevella, Shravya Ginnaram, Kamel Samara, Sai Shilpitha Janga, Robert Watson
Journal: Circulation (2024)

Background: Heart failure (HF) affects 6.7 million Americans and causes 500,000 deaths annually. Despite advancements in treatment, the 1-year mortality in advanced HF is 25-50%. Implantable left ventricular assist devices (LVAD) are critical for bridge-to-transplant or destination therapy, with 1-year and 2-year survival rates of 80% and 70%, respectively. At least 67% of LVAD patients have palliative care (PC) needs. However, PC involvement rates have been variable. The aim of this study is to measure the utilization of PC focusing on demographic disparities. Methods: Data was obtained from the National Inpatient Sample (NIS) 2021 database to identify patients with a principal diagnosis of HF (ICD I50.xx), secondary diagnoses of LVAD placement (Z45.2, Z95.811) and utilization of PC during encounter (Z51.5). Analysis was performed using SPSS statistical software. Results: Out of 5,688,355 adult hospitalizations in 2021, 1,048,573 patients were hospitalized with a primary diagnosis of HF. About 7.46% of HF patients received PC. Among these, patients over 75 years old, who constituted 44.4% of the cohort, accounted for 62.6% of PC involvement. PC consultation rates were similar between sexes. White patients made up 67.8% of the HF population but represented 73.6% of PC consultations, while other minority groups had a lower proportion of PC consultations. LVADs were implanted in 0.09% of HF patients, with 69.5% between 50-74 years old. A significant gender disparity was noted; 76.6% of LVAD recipients were male, and 23.4% female. PC was only involved in the care of 17.2% of LVAD patients. Age distribution of LVAD patients PC mirrored the overall LVAD cohort. Gender disparity persisted, with 80.4% of LVAD patients receiving PC being male, and 19.6% female. Racial disparities were less pronounced in this group. Conclusion: Despite proven benefits of PC involvement on the quality of life, psychological well being, and advanced care planning, specific guidelines in LVAD patients are yet to be established. This study underscores the need for more comprehensive guidelines promoting PC integration in the management of LVAD patients, and highlights demographic disparities in PC utilization among HF and LVAD patients.
Abstract 4139615: X-linked LAMP2B p.Val397Ile variant leads to late-onset Danon disease in females with hypertrophic cardiomyopathy
Authors: Alex Tran, Victoria Yuan, Kazuhiro Omi, Judy Fan, Sunny Chang, Jessica Wang
Journal: Circulation (2024)

Introduction: Danon disease is an X-linked dominant disorder in lysosome-associated membrane protein 2B (LAMP2B) that presents with cardiomyopathy and in males, intellectual disability. Dysfunction of LAMP2B, a lysosomal transmembrane protein in muscle, prevents macroautophagy and causes intracytoplasmic accumulation of cellular debris. Loss-of-function mutations in LAMP2B manifest as full Danon disease while missense mutations drive milder phenotypes. There is currently no effective therapy. Existing literature reports two transmembrane missense mutations, which presented as late-onset cardiac hypertrophy, but do not explore mutation pathogenicity. In our work, we investigate the mechanism of a novel transmembrane missense variant p.Val397Ile in two unrelated females who presented with late-onset hypertrophic obstructive cardiomyopathy with patient myectomy sample. Methods: Myectomy heart tissue was analyzed via Western blot and RT-qPCR for protein and RNA levels. In vitro overexpression of reference and alternate missense alleles was conducted in HEK293 cells, then analyzed by Western blot, RT-qPCR, and immunofluorescence. Immunofluorescence image analysis compared LAMP2B signal intensity and distribution between variant and wild-type proteins. Results: Patient heart tissue showed increased LAMP2 degradation and decreased autophagy markers by Western blot. EndoH treatment to investigate N- linked glycosylation patterns further revealed decreased total LAMP2 in patient samples. RT-qPCR showed increased RNA expression in the variant allele. LAMP2 overexpression in HEK293 cells resulted in reduced LAMP2B molecular weight and subcellular mislocalization. Fluorescent image segmentation revealed increased aggregation of variant LAMP2B around nuclei and surrounding structures compared to wild-type. Collectively, these results suggest arrested protein maturation in the Golgi apparatus and increased RNA expression to compensate for reduced functional protein. Conclusion: Our study demonstrated that the LAMP2B missense variant c.1189G&gt;A p.Val397Ile is implicated with increased degradation of LAMP2B protein, reduced protein levels of autophagy markers, and elevated LAMP2B RNA expression in cardiomyocytes. Our in vitro studies suggest that missense mutations may cause myocardial dysfunction via abnormal LAMP2B maturation and localization. Our work enhances mechanistic understanding of LAMP2B-related pathogenicity and may inform future therapeutic strategies for Danon disease.