tbuckley/cabot-search huggingface dataset:
Abstract 12911: Life’s Essential 8 and Heart Failure: The Million Veteran Program
Authors: Yanping Li, Xuan-Mai T Nguyen, Timothy M Treu, Dong D Wang, Yuk-lam Ho, Serena Houghton, Daniel Posner, SRIDHARAN RAGHAVAN, Mary Pyatt, David Gagnon, Stacey B Whitbourne, John Gaziano, Luc Djousse, Jacob Joseph, Peter Wilson, Kelly Kim
Journal: Circulation (2023)

Background: Heart failure (HF) incidence has increased over past decades and is associated with poor quality of life, increased comorbidities, and high treatment costs. Prevention for HF warrant a major public health priority. Aim: To quantify the association of Life’s Essential 8 (LE8) score with HF. Methods: LE8 score (0-800) was developed based on the AHA guidelines among 348,311 Veterans who enrolled in the VA Million Veteran Program (MVP) (2011-2021) and free of HF at baseline. Cox proportional hazard models were used to calculate the hazard ratios (HR) with their 95% confidence intervals (CI) for first incident HF event, and HF subtypes (HF with reduced ejection fracture (HFrEF) and HF with preserved EF (HFpEF)) across categories of LE8 score. The population attributable fraction (PAF) was calculated to estimate the proportional reduction in HF events that would occur if LE8 was changed to the ideal level. Results: A total of 31,397 HF events were recorded over 1.8 million person-years of follow-up. LE8 score was negatively associated with incidence of HF, HFrEF and HRpEF, even after extensive adjustment for potential confounders ( Figure 1A ). The multivariate-adjusted HR for HF was 0.76 (95% CI: 0.73-0.78), 0.63 (0.61-0.65), 0.52 (0.50-0.54), 0.41 (0.39-0.43), 0.34 (0.32-0.36), 0.28 (0.27-0.30), and 0.23 (0.21-0.25), respectively, among Veterans whose LE8 score was 350-, 400-, 450-, 500-, 550-, 600- and ≥650, respectively, as compared to those with LE8 score &lt;350. The PAF for HF was 7.1%, 10.3%, 15.1%, 15.8%, 17.1%, 17.5% 18.4%, and 49.1% for not ideal sleep, diet, lipid, activity, BMI, smoking, glucose/HbA1c, and blood pressure, respectively, with an estimated joint PAF of 83.2% for total HF, 79.5% for HFrEF and 90.1% for HFpEF for not ideal of any LE8 ( Figure 1B ). Conclusion: Greater adherence to a healthy LE8 lifestyle could be a key component in prevention of HF among Veterans. Assuming everyone follows a lifestyle meet ideal LE8, majority of HF cases will be prevented.
Abstract 11710: The Integrative Experimental and Computational Approach to Assess Patient Lipid-Lowering Drug Adherence for Coronary Artery Disease Risk Diagnostics
Authors: Anna A Ivanova, Jennifer Kusovschi, Michael Gardner, William E Kraus, Robert McGarrah, Zsuzsanna Kuklenyik, John R Barr
Journal: Circulation (2023)

Background: Statins, lipid-lowering drugs, are the first-line pharmaceutical therapy against Atherosclerotic Cardiovascular Disease (ASCVD). The emphasis on providing statin treatment as a preventive measure before the first cardiac event burdens low-risk individuals with adverse side effects. Furthermore, inaccurate self-reporting of statin use by patients or their poor adherence to statins complicates the monitoring of long-term benefits and side effects of statins and ASCVD risk assessment. New sensitive, multiplexed and high throughput methods to confirm actual statin use by patients are urgently needed. Methods: We used 690 plasma samples from individuals with known number of diseased vessels, established lipid profiles, and medication records of statin use. The samples were obtained from the CATHeterization GENetics (CATHGEN) sample archive. The levels of 7 statins (atorvastatin, simvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and fluvastatin) in the plasma samples were determined by a 4-minute-long Liquid Chromatography-Mass Spectrometry Method (LC-MS/MS). Nominal logistic regression algorithms were employed to model coronary artery disease (CAD) outcomes with the incorporation of statin use, phenotypic, and lipid profile characteristics. Results: Our LC-MS/MS analysis has revealed discrepancies between the reported statin medication use and the detected statin levels in plasma. The reported statin use history was confirmed for 212 out of 261 patients. Among 429 specimens without a recorded history of statin use, statin was detected in 198 specimens. Comparison of logistic regression models built with statin use data as a covariate and with stratification by statin users and non-users revealed significant differences in covariate corrected mean lipid profile measures and their association with predicted atherosclerosis outcomes. Conclusion: In summary, high-throughput multiplexed LC-MS/MS analysis is highly applicable to uncover discrepancies between the self-reported and actual use of statins. By combining LC-MS/MS with statistical modeling, we showed that these discrepancies may significantly affect the modeled association between lipid profile measures and ASCVD outcome.
Abstract 11716: Patent Foramen Ovale Closure vs Medical Therapy in Patients ≥ 60 Years of Age With Ischemic Stroke: A Retrospective Cohort Study
Authors: Andres Cordova Sanchez, Bharat Rawlley, Sherna Menezes, Ana Morales Mejia, Kenneth Adames Ramos, Debanik Chaudhuri
Journal: Circulation (2023)

Background: The benefit of patent foramen ovale (PFO) closure in patients aged ≥60 years with ischemic stroke is uncertain. Purpose: We conducted a retrospective cohort study to compare the outcomes of PFO closure vs medical therapy in this population. Methods: Using the TriNetX research database we identified patients ≥ 60 years with PFO who had an ischemic stroke from 2016 to 2021. Patients were divided into two groups: those undergoing PFO closure within 3 months of the stroke and those who received medical therapy only. Subgroup analyses was performed by age group (60 to 70 and ≥71). Propensity score matching was used to control for age, sex, hypertensive diseases, CKD, diabetes, dyslipidemias, ischemic heart disease, tobacco use, and neoplasms. Outcomes were measured from 1 month to 3 years after the index event and included all-cause mortality, new onset AF/flutter, arterial embolism, and services associated with stroke/embolism (thrombolysis, thrombectomy, administration of thrombolytics, and imaging of head and neck). Results: PFO closure was associated with lower number of services used in stroke/embolism (HR 0.57, 95%CI 0.42-0.78), a similar association was seen in those in the 60-70 age group (HR 0.539, 95%CI 0.373,0.78) but not in those ≥71 years. Arterial embolism was seen in 3.14% of the patients who received antiplatelets or anticoagulants only, but none of the patients who underwent PFO (Table 1) . Conclusions: PFO closure was associated with lower number of services used in stroke/embolism in patients aged ≥60 years with ischemic stroke. Our study could have been underpowered to find differences amongst those ≥71 years old. None of the patients who underwent PFO closure developed arterial embolism. PFO closure may be beneficial for older patients with ischemic stroke and warrant further investigation
Abstract 12116: Identifying the Underlying Causes of Unexplained Dyspnea at High Altitude Using Normobaric Hypoxia With Transthoracic Echocardiography
Authors: Jan Stepanek, Ahmed K. Mahmoud, JUAN M FARINA, Chieh-Ju Chao, Said Alsidawi, Chadi Ayoub, Timothy Barry, Rachel E Wraith, Lisa S Brown, Michael S Radavich, Pamela J Curtisi, Patricia C Hartzendorf, Elizabeth M Lasota, Kyley N Umetsu, Jill M Peterson, Kristin E Karlson, Karen K Breznak, BSN, Steven J Lester, Reza Arsanjani
Journal: Circulation (2023)

Introduction: Exposure to high altitude results in hypobaric hypoxia, leading to physiological changes in the cardiovascular system that may result in dyspnea. Hypoxic simulation testing (HSTs) simulates changes in physiology that occur at a specific altitude. Hypothesis: The use of transthoracic echocardiography (TTE) during HST can detect the raise in right-sided pressures revealing underlying causes of high-altitude dyspnea. Methods: We performed a prospective observational study of consecutive patients with unexplained dyspnea at high altitude who were referred to an aerospace medicine program at a single institution between August 2021 and March 2023. Reduced FiO 2 was administered for 20 minutes to simulate altitude levels specific to patients’ history. TTE images were obtained at baseline and during peak hypoxia to evaluate right ventricular (RV) function, RV systolic pressure, and any possible shunts. Result: The study included 27 patients, with a mean age of 64.7 ±14.4 years and 14 (51.9%) females. No significant abnormalities were seen on baseline TTE and no significant differences in blood pressure and heart rate between baseline and hypoxia simulation were detected. Notably, RV systolic pressure increased at peak hypoxia, while RV systolic function declined as shown by a decrease in S’ wave and TAPSE ( Figure 1 ). Additionally, right to left shunts were present in 19 (70.4%) patients. Of these, four patients (21.1%) had shunts present at baseline with no changes at peak hypoxia, while the severity of shunts increased at peak hypoxia in eight cases (42.1%) and the shunts were only evident during hypoxia in seven patients (36.8%). Conclusion: TTE during HST provides valuable information by revealing the presence of symptomatic, sustained shunts and confirming the decline in RV hemodynamics explaining dyspnea at altitude. Further studies are necessary to establish the optimal clinical role of this physiologic method.
Abstract 12914: Echocardiographic Assessment of Ventricular Stiffness in Single Right Ventricle Physiology: A Validation Study
Authors: Shahryar M Chowdhury, Donald R Menick, Varsha Bandisode, John Rhodes, Eric M Graham, Andrew M Atz
Journal: Circulation (2023)

Background: Ventricular stiffness is associated with outcomes in patients with single right ventricle (SRV) physiology. However, echocardiographic (echo) assessments of ventricular stiffness are limited in this population. The objective of this study was to assess if echo measures of diastolic function are associated with invasive reference standard measures of ventricular stiffness derived from pressure-volume loop (PVL) analysis. Methods: Patients with SRV physiology undergoing pre-Fontan heart catheterization were prospectively enrolled. PVLs were obtained via microconductance catheters. The reference standard measure of ventricular stiffness, β, was obtained after balloon occlusion of the vena cavae. Echo measures were derived from spectral and tissue Doppler and 3D echo. Conceptually, patients with abnormal active ventricular relaxation and small end-diastolic ventricular volumes (EDV) are at risk for having increased passive ventricular stiffness. Therefore, the echo measurement of interest was lateral E:e’ divided by EDV indexed to body surface area (E:e’/EDVi). Results: 19 patients included in the study. Mean age was 4.1 ± 0.7 years. Median β was 0.022 mL -1 (IQR 0.012, 0.062). Median lateral E:e’/EDVi was 0.10 mL -1 /m 2 (IQR 0.07, 0.15). The correlation between lateral E:e’/EDVi and β was r = 0.65, p &lt; 0.01 (Figure). No other correlations existed between echo measures of diastolic function and invasively derived ventricular stiffness. Conclusion: Lateral E:e’/EDVi correlates reasonably well with the reference standard measure of ventricular stiffness in SRV patients prior to the Fontan operation. The clinical utility of assessing lateral E:e’/EDV in SRV patients should be further explored regarding its potential to identify novel insights into the pathophysiology of SRV heart disease, detect changes in stiffness after medical/surgical intervention, and to investigate new echo predictors of outcome.
Abstract 11740: Redefining Cardiac Involvement in Systemic Immunoglobulin Light Chain Amyloidosis and Treatment Implications
Authors: Aldostefano Porcari, Ambra Masi, Ana Martinez-Naharro, Yousuf Razvi, Rishi Patel, Adam Ioannou, Muhammad Rauf, Giulio Sinigiani, Brendan Wisniowski, Stefano Filisetti, Jasmine CURRIE-CATHEY, Sophie O'Beara, Tushar Kotecha, Daniel Knight, James Moon, Gianfranco sinagra, Ruta Virsinskaite, Janet A GILBERTSON, Lucia Venneri, Aviva Petrie, Helen Lachmann, Carol Whelan, Peter Kellman, Sriram Ravichandran, Oliver Cohen, Shameem Mahmood, Philip N Hawkins, Julian D Gillmore, Ashutosh Wechalekar, Marianna Fontana
Journal: Circulation (2023)

Introduction: Cardiac amyloidosis (CA) is the key determinant of survival in systemic AL amyloidosis. Hypothesis: To assess (i) the differences between serum biomarkers, echocardiography and CMR with ECV mapping in characterising cardiac involvement, (ii) their independent prognostic role, and (iii) the role of ECV mapping to guide treatment strategies. Methods: Consecutive patients newly diagnosed with systemic AL amyloidosis between 2015-2021 who underwent echocardiography, cardiac biomarkers, and CMR with ECV mapping at the time of diagnosis were included. Haematological response (HR) at 1 and 6 months was defined according to validated criteria. The primary outcome was mortality. Results: Five-hundred sixty AL patients were included. The different approaches produced different results in terms of presence and severity of cardiac infiltration (CA present from 48.2% to 93%). Over 40.5 months [IQR 9-58], only ECV was independently associated with mortality (p&lt; 0.001). In the landmark analysis at 1 month, patients with ECV &lt; 0.30 and with ECV 0.31-0.40 had an excellent long-term survival regardless of the achieved HR (p=0.92 and p=0.08, respectively), whilst in patients with ECV &gt; 0.40 survival was dependent on the depth of the HR (p&lt; 0.001). In the landmark analysis at 6 months, patients with ECV &lt; 0.30 had excellent survival regardless of the achieved HR and patients with ECV 0.31-0.40 had excellent survival if achieving at least a PR (inter-group p=0.006 in NR vs PR). In ECV 0.41-0.50 and ECV &gt; 0.50, long-term survival was excellent only among patients achieving CR (inter-group p&lt; 0.05 in CR vs VGPR). Reaching a deep HR at 1 month vs 6 months was associated with better survival in ECV &gt; 0.40 (p&lt; 0.05), but not in ECV &lt; 0.40. Conclusions: ECV mapping in systemic AL amyloidosis is the only independent predictor of prognosis. ECV mapping can define optimal depth and rapidity of the HR for each patient and inform treatment strategies.
Abstract 12266: CCND2 Modified mRNA Activates the Cell Cycle in Cardiomyocytes and Improves Recovery From Myocardial Infarction in Small and Large Mammals
Authors: Jiacheng Sun, Lu Wang, Yang Zhou, Jianyi J Zhang
Journal: Circulation (2023)

Background: Experiments in mammalian models of cardiac injury suggest that the cardiomyocyte (CM)-specific overexpression of cyclin D2 (CCND2 in humans) improves recovery from myocardial infarction (MI). The primary objective of this investigation was to demonstrate that our Specific Modified mRNA Translation System (SMRTs) can induce CCND2 expression in CMs (CCND2-CMs) and replicate the benefits observed in other studies of CM-specific CCND2 overexpression for myocardial repair. Methods: The CCND2-CM SMRTs consists of two modRNA constructs: one codes for CCND2 and contains a binding site for L7Ae, and the other codes for L7Ae and contains recognition elements for the CM-specific microRNAs miR-1 and miR-208. Thus, L7Ae suppresses CCND2 translation in noncardiomyocytes but is itself suppressed by endogenous miR-1 and -208 in CMs, thereby facilitating CM-specific CCND2 expression. Experiments were conducted in both mouse and pig models of MI, and control assessments were performed in animals treated with an SMRTs coding for the CM-specific expression of luciferase or GFP, in animals treated with L7Ae modRNA alone or with the delivery vehicle, and in Sham-operated animals. Results: CCND2 was abundantly expressed in cultured, post-mitotic CMs two days after transfection with CCND2-CM SMRTs, and the increase was accompanied by the upregulation of markers for cell-cycle activation and proliferation (e.g., Ki67 and Aurora B kinase). When the GFP-CM SMRTs was intramyocardially injected into infarcted mouse hearts, the GFP signal was observed in CMs but no other cell type. In both the mouse and pig MI models, CM proliferation (on Day 7 and Day 3 after treatment administration in mice and pigs, respectively) was significantly greater, left-ventricular ejection fractions (Days 7 and 28 in mice, Days 10 and 28 in pigs) were significantly higher, and infarcts (Day 28 in both species) were significantly smaller in animals treated with CCND2-CM SMRTs than in any other group that underwent MI induction. Conclusion: Intramyocardial injections of the CCND2-CM SMRTs promoted CM proliferation, reduced infarct size, and improved cardiac performance in small and large mammalian hearts with AMI.
Abstract 12107: Cardiovascular Outcomes Associated With Gonadotropin-Releasing Hormone Antagonists vs Gonadotropin-Releasing Hormone Agonists for Prostate Cancer Treatment: A Meta-Analysis of Randomized Controlled Trials
Authors: Vikash Jaiswal, Akash Jaiswal, Marina Saleeb, Mayank Jha, Muhammad Hanif, Kriti Kalra, Endurance O Evbayekha, Vibhor Agrawal, Song Peng Ang, Jerome S Zacks
Journal: Circulation (2023)

Background: Androgen deprivation therapy (ADT), comprising the administration of Gonadotropin-releasing hormone (GnRH) agonists and antagonists, is a widely utilized treatment for prostate cancer patients and has been universally accepted as the first-line treatment for symptomatic metastatic prostatic cancer. While ADT has proven effective, concerns about its impact on cardiovascular health have emerged. Conflicting results regarding the association between ADT and cardiovascular events have been reported in the most recent PRONOUNCE trial hence a meta-analysis to systematically evaluate the evidence is desired. Aim: The primary objective of this meta-analysis was to investigate and compare the effects of GnRH agonists and antagonists on cardiovascular events in patients with prostate cancer. Methods: A comprehensive search was conducted in major electronic databases to identify relevant RCTs. Studies published from inception to April 2023 were scrutinized. Results: 9 studies met the eligibility criteria and were included in the final analysis. A total of 3648 patients were randomized to receive either an agonist (n=1375) or an antagonist (n=2273). The pooled results revealed a significant reduction in the risk of adverse cardiovascular events by 48% with the use of GnRH agonists compared to GnRH antagonists (RR=0.52; 95% CI=0.39-0.71; p&lt;0.01). Furthermore, GnRH agonists also decreased the risk of all-cause mortality by 46% (RR=0.54; 95% CI= 0.33-0.88; p=0.01) and cardiovascular mortality by 78% (RR= 0.22; 95% CI= 0.07-0.76; p=0.02) compared to GnRH antagonists. Conclusion: The findings of this meta-analysis reveal the favorable cardiovascular risk profile associated with GnRH agonists, supporting their role as a preferred treatment option over GnRH antagonists.
Abstract 12931: Development of Novel Targeted, Membrane-Coated Polymer Hybrid Nanoparticles for Endothelial Repair Following Balloon Angioplasty in Rat Carotid Artery Model
Authors: Lalithasri Ramasubramanian, Nataliya Bahatyrevich, Dake Hao, Christopher Pivetti, Emma G Loll, Zachary J Paxton, Siraj S Gidda, Priyadarsi Kumar, Diana L Farmer, Alyssa Panitch, Aijun Wang
Journal: Circulation (2023)

Background: Coronary and peripheral arterial disease remains one of the leading causes of death worldwide. Treatments include balloon angioplasty, stent placement, or bypass grafting, all of which damage the endothelium and increase the risk of thrombosis or intimal hyperplasia. Thus, there is a critical need for rapid reendothelialization following these treatments. Endothelial progenitor cell-derived (EPC) extracellular vesicles (EVs) containing proangiogenic microRNAs, such as miR126, is one of the natural mechanisms of vascular repair. However, the translational application of EVs is limited by low EV yield, functional heterogeneity, and difficult tissue targeting. Hypothesis: We hypothesize that EV-inspired hybrid nanoparticles can improve reendothelialization and modification with a specific collagen binding peptide SILY can target vascular injury. Aims: (1) Engineer and characterize a SILY modified hybrid EPC membrane coated nanoparticles (SILY-ENPs) containing a miRNA-126-loaded poly-lactic-co-glycolic acid core (miR126-PLGA) in vitro . (2) Test the therapeutic efficacy of the SILY-ENPs in an in vivo rat carotid balloon angioplasty model. Methods: EPC plasma membranes were isolated from umbilical cord blood EPCs and conjugated with SILY using copper-free Click chemistry. Membrane fragments were coextruded with miR126-PLGA to form SILY-ENPs. Particles were characterized in vitro for collagen and platelet binding and angiogenic function. In vivo function was tested in a rat carotid balloon angioplasty model. Results: SILY-ENPs were found to have increased collagen binding and decreased platelet activity. Delivery of miR126 cargo slightly improved pro-angiogenic protein expression and increased rates of reendothelialization. However, SILY-ENPs were found to stimulate hyperplasia as an adverse side-effect. Conclusions: SILY-ENPs exhibited target specificity, decreased platelet activity, and increased rates of reendothelialization, but increased intimal hyperplasia. This technology represents a novel EV inspired nanoplatform which can be tailored for treating various diseases by altering the cargo or membrane coating.
Abstract 11450: The Association of Care Fragmentation on Limb Outcomes After Endovascular PAD Procedures Requiring Reintervention
Authors: Olamide Alabi, Xinyan Zheng, Yazan Duwayri, Jialin Mao, NADER MASSARWEH
Journal: Circulation (2023)

Introduction: Several policies exist that incentivize improved care coordination. Reintervention care fragmentation (when a patient requires a reintervention at another facility that is different than the index facility) for peripheral artery disease (PAD) has not been well-characterized. The intent of this work is to explore the frequency, characteristics, and differences in outcomes for patients when a vascular reintervention occurs at a non-index facility. Methods: National cohort of adults over age 65 who underwent an endovascular procedure for PAD within the Vascular Quality Initiative between January 1, 2010 to December 31, 2018 and had subsequent vascular reintervention. Data was linked to Medicare claims and American Hospital Association. We excluded emergency procedures, those performed for aneurysm, and those performed in an office-based setting. The primary outcomes were 90-day and 180-day amputation. Covariates of interest included sociodemographic, anatomic, procedural, and facility-level characteristics. Mixed effect logistic regression models (clustered at the facility-level) were used to determine the association between reintervention at an index versus non-index facility and the outcomes of interest. Results: Among 4,470 patients who underwent a vascular reintervention after an index endovascular procedure for PAD, 18.1% had their reintervention performed at a non-index facility. There were no differences noted by sex or level of community distress among those who went to the index facility versus a non-index facility for their vascular reintervention. Compared to those who had their reintervention at an index facility, vascular reintervention at a non-index facility was associated with significantly higher likelihood of major amputation (90-d amputation: Odds Ratio (OR) 1.61 [95% Confidence Interval (CI) 1.08-2.39]; 180-day amputation: OR 1.75 [95% CI 1.14-2.70]). Conclusions: Care fragmentation for patients who require vascular reintervention after an index endovascular PAD procedure is associated with higher risk of amputation. Additional work is needed to better understand which patients are at greatest risk for care fragmentation and how to better coordinate care in the post-procedural setting.