tbuckley/cabot-search huggingface dataset:
Abstract 15047: The Probability of miRNA Derived From Extracellular Vesicles as Functional Biomarkers for Patients With Lower Extremity Artery Disease
Authors: Naoya Kuriyama, Shinsuke Kikuchi, Yusuke Yoshioka, Juntaro Matsuzaki, Nobuyoshi Azuma, Takahiro Ochiya
Journal: Circulation (2023)

Introduction: Lower extremity artery disease (LEAD) is a progressive and systematic manifestation of atherosclerosis. In LEAD, multiple arterial beds are affected increasing the possibility of death due to coronary artery disease (CAD) and cerebrovascular disease (CVD). We have identified functional biomarkers that can be used to predict clinical outcomes in patients with LEAD by analyzing miRNAs contained in the extracellular vesicles (EVs). Methods: A total of 146 patients with diabetes and without end-stage renal disease were enrolled as research subjects between 2019 and 2021. Among them, 118 had LEAD, including 6 asymptomatic cases, 43 cases of claudication, and 69 cases of chronic limb-threatening ischemia (CLTI). The remaining 28 cases were in the Control group, who were systematically screened for atherosclerotic lesions by radiological modalities. We performed miRNA sequencing using the EV-derived miRNAs from patients’ serum. We developed machine learning based models to diagnose LEAD, CLTI, CAD, and CVD. We used Cox models to identify miRNAs associated with the patency rate at the reconstruction site, amputation-free survival (AFS), and major cardiovascular events (MACE). Results: The area under curve (AUC) of the diagnostic models for LEAD, CLTI, CAD, and CVD for the training data were 0.82, 1.00, 1.00, and 1.00, respectively, and for the test data were 0.68, 0.85, 0.71, and 0.51, respectively. The diagnostic model for CLTI showed the highest generalization performance among these models. We performed pathway analysis for miRNAs with fold change &gt; 2 in CLTI using DIANA-miRPath v3.0, which revealed enrichment of proteoglycans in cancer, Wnt signaling, and TGF-beta signaling pathways.We identified 62 miRNAs as significant risk factors affecting the patency. The group with has-miR-6850-3p above the median (78.8%) had significantly higher one-year patency rate compared to the group with has-miR-6850-3p below the median (59.5%) (p = 0.03). In addition, we identified 6 and 4 miRNAs as risk factors related to AFS and MACE, respectively. Conclusions: EV miRNAs have high potential as biomarkers for predicting prognosis, treatment outcome, and other atherosclerotic lesion associated with LEAD in the diabetic patients.
Abstract 15278: Cardiac Assessments and Manifestations Among Individuals With Long-Chain Fatty Acid Oxidation Disorders: A Retrospective Claims Database Analysis
Authors: Julian Mesa, Erru Yang, Kate Simmons, Deborah Marsden, Kathryn C Chatfield
Journal: Circulation (2023)

Introduction: Long-chain fatty acid oxidation disorders (LC-FAOD) are inherited autosomal recessive defects resulting in enzyme deficiencies in the carnitine cycle or the mitochondrial β-oxidation pathway leading to deficiencies in mitochondrial energy metabolism. Cardiac manifestations, specifically cardiomyopathy and arrhythmias, are common and are leading causes of mortality in individuals with LC-FAOD. Goal: The goal of this study was to better understand cardiac manifestations and long-term outcomes in this group of disorders. Methods: The analysis was done using IQVIA PharMetrics® claims data. Individuals with confirmed LC-FAOD were identified and a non-LC-FAOD comparators group was created using 1:20 exact matching on age, gender, payer type, and enrollment start year. Cardiac-related complications were examined using ICD-10 diagnosis codes at any billing position during the study period. Cardiac diagnoses and assessments were evaluated using Current Procedural Terminology (CPT®) codes in a non-inpatient setting. Results: A total of 337 pediatric (peds) and 86 adult individuals with LC-FAOD were included in the study. Cardiomyopathy (peds: 8.0%, adults: 10.5%) and arrhythmias (peds: 8.9%, adults: 14.0%) were common among individuals with LC-FAOD and were significantly higher than comparators. LC-FAOD adults had significantly more cardiac conditions compared with pediatric patients and comparators. The other most common cardiac conditions among adults with LC-FAOD were chronic ischemic heart disease (18.6%), non-rheumatic mitral or tricuspid valve disorders (11.6% and 12.8%, respectively), heart failure (10.5%), atrioventricular and left bundle-branch block (7.0%), and cardiomegaly (5.1%). Individuals with LC-FAOD had significantly more cardiac related procedures than comparators. EKGs (peds: 35.9%; adults: 77.9%) and echocardiograms (peds: 44.8%; adults: 53.5%) were common among individuals with LC-FAOD. Conclusions: This analysis shows the importance of assessing the cardiac status of individuals with LC-FAOD. More analyses and natural history studies are needed to inform healthcare providers of cardiac risks associated with LC-FAOD and reduce mortality in these individuals.
Abstract 18974: Transcatheter Tricuspid Valve Replacement in a Symptomatic Bioprosthetic Tricuspid Stenosis Patient With Carcinoid Heart Disease: A Case Report
Authors: SUMA PUSAPATI, Sowjanya Kapaganti, Arun R Kanmanthareddy
Journal: Circulation (2023)

Background: Patients with carcinoid heart disease are prone to the development of mild to severe tricuspid regurgitation with or without accompanying tricuspid stenosis. We present an interesting case of a patient with bioprosthetic tricuspid valve stenosis secondary to carcinoid heart disease undergoing transcatheter tricuspid valve replacement (TTVR). Case history: The patient is a 64-year-old female with metastatic carcinoid syndrome and subsequent tricuspid valve replacement with 25 mm Magna ease bovine pericardial valve. The surgery was complicated by carcinoid crisis, pneumothorax, and complete heart block. She presented with worsening shortness of breath with exertion. Echocardiography revealed severe tricuspid stenosis associated with a severely dilated right atrium, moderate pulmonary stenosis. Transesophageal echocardiography confirmed carcinoid degeneration of the bioprosthetic tricuspid valve. CT chest and abdomen with contrast showed consistent findings of severe tricuspid stenosis, metastatic carcinoid tumor with new foci in liver, lungs. Ischemic evaluation with angiography revealed normal coronaries. Decision making: The patient was evaluated by the heart team and was considered to be a prohibitive risk patient for redo surgery. We then evaluated her suitability for transcatheter valve replacement, and the patient was felt suitable for undergoing valve-in-valve transcatheter tricuspid valve replacement via the right internal jugular vein approach because of the coaxial alignment of the valve through this route. The patient successfully underwent this procedure with a 26 mm balloon-expandable valve without any complications and is currently in NYHA class I functional status. Conclusion: Carcinoid syndrome can affect bioprosthetic tricuspid valves and transcatheter valve replacement may be advantageous in replacing the affected bioprosthetic valves by reducing morbidity and mortality.
Abstract 17875: Quality Improvement Initiative to Improve Screening and Diagnosis Rates of Iron Deficiency in Patients Hospitalized for Acute Heart Failure With Reduced Ejection Fraction
Authors: Roopesh Sai Jakulla, Ifrah Fatima, Preetham Gunta, Keerat Gill, Mohammed S Mohammed, Marwa Elsayed, Tatiana Tselovalnikova, Amandeep Goyal, Poonam Bhyan, Siva Naga S Yarrarapu, Lakshmi Priya, Julie Banderas, David Wooldridge, Angel Lopez-candales
Journal: Circulation (2023)

Introduction: Despite being associated with reduced exercise capacity and poor quality of life in HFrEF, iron deficiency (ID) is underdiagnosed and undertreated. The 2022 ACC/AHA guidelines define ID in HFrEF as either a serum ferritin level &lt; 100 ng/ml or 100-299 ng/ml with transferrin saturation (TSAT) &lt;20 %. Treatment with IV iron is associated with a reduced risk of hospitalizations for HFrEF. A review of 20 inpatient acute HFrEF records revealed 10 had iron studies ordered, and 9 of them met criteria for ID, but only 1 patient received IV iron. Aim statement: To improve the testing rates for ID in hospitalized acute HFrEF patients at our hospital by 10% from January through March 2023. Methods: QI project included the implementation of an electronic health record (EHR) alert (Fig. 1) and resident education. The EHR alert was designed to be activated at the time of admission for patients with specific ICD codes for acute HFrEF to aid in ordering iron studies. A 20-minute educational session was delivered to residents, and handouts were provided to residents with reference material. Results: Pre-intervention data from January-December 2022 revealed a testing rate of 68% (154/194). ID was present in 58% (113/194). Post-intervention data from January 2023-March 2023 showed an improvement in the testing rate to 91% (67/73) and a concurrent increase in the diagnosis rate to 72% (53/73) (Fig. 2). Before discharge, 43.4% of patients (23/53) with ID received IV iron sucrose. Conclusion: Education and implementation of EHR alert were successful in increasing the testing rates for ID in acute HFrEF irrespective of anemia status. EHR tools should enhance sustainability compared to education alone.
Abstract 18216: NT-proBNP After Discharge in Patients With Decompensated Heart Failure and Preserved Left Ventricle Ejection Fraction: The NICE Study
Authors: Domingo Pascual Figal, Adrián Gallego Navarro, Javier E. Blanco Pacheco, Maria Martinez-Tovar, Álvaro Hernández Vicente, Manuel Martínez Selle, Eduard Solé González, Pedro Luis Sánchez Fernández, Pablo García Pavía, Alfonso Varela Román, Juan Fco. Delgado Jiménez, Alejandro Riquelme Perez, José A Noguera Velasco, Jordi Ordóñez Llanos, Antoni Bayés Genís
Journal: Circulation (2023)

Introduction: In hospitalized patients with heart failure (HF), the transition period after discharge is associated with high risk of adverse events. The impact of monitoring natriuretic peptides (NP) in patients with preserved LVEF (HFpEF) has not specifically studied. Methods: NICE trial (NCT02807168) is a randomized, open-label, blinded for events and multicenter study. The study population included hospitalized patients with HFpEF (LVEF&gt;50% and at least one additional criteria of diastolic dysfunction). Patients were randomized at discharge into intervention (NP group) or control group. Both groups received optimal therapy and scheduled clinical visits at 14 and 30 days, 3 and 6 months, and NT-proBNP results were available for the clinician only in the intervention group. Results: 157 patients (76±8 years, 61% female, LVEF 61±7%) were randomized into NP group (n=79) and control group (n=78). Baseline characteristics did not differ between groups. At 6 months, no differences were found in HF readmission in NP vs. control group (12.8% vs. 11.4%, HR 1.15, CI95% 0.47-2.81), or any episode of worsening HF (20.5% vs. 24.1%, HR 0.89, CI95% 0.44-1.82). NP group had a significantly lower mortality than the control group (1.3% vs. 10.1%, HR 0.12, IC95% 0.02-0.98, p=0.048), as well as a trend to lower risk of hospitalization for non-HF related causes (12.8% vs. 19.0%, HR 0.68, IC95% 0.39-1.18). Considering the composite end-point (death or worsening HF), the intervention with NT-proBNP was associated with a lower risk trend (20.5% vs. 30.4%, HR 0.65, IC95% 0.34-1.22, p=0.181). Regarding the use of medical therapies, diuretic and ACEI doses were higher in the intervention group during the follow-up. Conclusions: In hospitalized patients with HFpEF, NT-proBNP availability during the transition period did not reduce the risk of HF readmissions. Nevertheless, it was associated with a lower mortality. These results suggest a global impact in the disease, beyond readmissions.
Abstract 18376: Social Vulnerability Indices as a Measure for the Impact of Social Determinants of Health on SGLT2-i Prescriptions in Patients With HFrEF
Authors: Anushree Puttur, Kyle Kapcin, Omar A Ta'ani, Abdallah Naser, Aaisha Shah, Divya Venkat
Journal: Circulation (2023)

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) are an important member of the 5 pillars of goal directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF) that was introduced in the 2022 AHA/ACC/HFSA heart failure guidelines. Despite the role of GDMT in reducing cardiovascular mortality and heart failure outcomes, medication accessibility remains limited among more socially vulnerable populations. Social Determinants of Health (SDoH) play a vital role in how patients receive and engage with health care. Goals/Aims: Our study aims to utilize the social vulnerability indices (SVI), an underutilized tool used to quantify social vulnerability, to determine associations between SDoH with SGLT2-i prescriptions. Methods/Approach: A retrospective review of SVI in 864 patients with a diagnosis of HFrEF in two urban Internal Medicine outpatient clinics between April 2022 and June 2023 was performed. Composite social vulnerability, as well as subgroups of individual data points utilized in the Centers for Disease Control and Prevention SVI were compared between those prescribed and not prescribed a SGLT2-i. Patients with a diagnosis of HFrEF were assigned SVI scores based on geocoded census tract level data. Chi-square analysis was performed to compare groups. A p-value less than &lt;0.05 was considered significant. Results: A total of 864 patients were evaluated. 78 of these patients were prescribed a SGLT2-i, while 786 were not prescribed a SGLT2-i. Those with a SVI overall percentile of 74-100% (less social vulnerability) were significantly more likely to be on a SGLT2-i (19.23% vs 10.02%, p = 0.022). Descriptively, patients with SVI Est &lt;24% below poverty were less often prescribed SGLT2-i (92.05% vs 7.95%). Similarly, those without a vehicle as defined by SVI Est &lt;24% households with no vehicle available were on less frequently prescribed SGLT2-i (93.24% vs 6.76%). Conclusion: Use of SVI data may help identify barriers to SGLT-2 prescribing in patients with HFrEF when analyzed on a population level. Further studies and investigations to target these barriers may be beneficial in increasing the amount of patients on indicated GDMT. Keywords: social determinants of health, SGLT-2i, GDMT, HFrEF
Abstract 14959: Impact of Timing of Venoarterial Extracorporeal Membrane Oxygenation Insertion (Before or After Impella) in Patients With Acute Myocardial Infarction With Cardiogenic Shock Using Impella: From J-PVAD Registry
Authors: Ryusuke Nishikawa, shin watanabe, Hiroki Shiomi, Munekazu Tanaka, Yugo Yamashita, Erika Yamamoto, Kyohei Yamaji, Koh Ono
Journal: Circulation (2023)

Introduction: In patients with cardiogenic shock (CS), Impella, one type of percutaneous ventricular assist device with a catheter-type micro-axial heart pump, plus venoarterial extracorporeal membrane oxygenation (ECPELLA) has been reported to have a better short-term prognosis than venoarterial extracorporeal membrane oxygenation (VA-ECMO) alone, although it was associated with more complications. ECPELLA has often been used in current clinical practice instead of VA-ECMO alone. However, in many cases of acute myocardial infarction (AMI) with CS, there is controversy about whether Impella or VA-ECMO should be installed first. Hypothesis: What are the factors associated with Impella use first? Does the timing of VA-ECMO insertion affect prognosis and major adverse events (MAEs) such as hemolysis, hemorrhage/hematoma, peripheral ischemia, stroke, and thrombosis? This study aims to clarify the factors of Impella use first and the prognostic impact of the timing of VA-ECMO insertion (before or after Impella). Methods: The Japanese registry for Percutaneous Ventricular Assist Device (J-PVAD) has registered all consecutive Japanese patients treated with Impella between February 2020 and December 2021. In the current study, we evaluated 523 patients with AMI with CS and investigated the factors of Impella use before VA-ECMO and the impact of the timing of VA-ECMO insertion on 30 days mortality and MAEs. Results: Out of the total number of patients, 155 (30%) received Impella prior to VA-ECMO, while 367 (70%) received Impella following VA-ECMO. The factors of Impella use before VA-ECMO were the absence of out-of-hospital and in-hospital cardiac arrest. The cumulative 30-day incidence of all-cause death was 46.1% in patients with Impella use before VA-ECMO and 53.5% in those with Impella use after VA-ECMO (Log-rank P=0.13). There was no excess risk of Impella use before VA-ECMO relative to Impella use after VA-ECMO (adjusted HR, 0.95; 95%CI, 0.47-1.94; P=0.90). There were no significant differences in the incidence of MAEs between the two groups. Conclusions: The prognosis for patients with AMI complicated by CS requiring ECPELLA remained poor, but the timing of VA-ECMO insertion did not affect the prognosis.
Abstract 17748: Lipoprotein(a) and Oxidized Phospholipids on Lipoproteins and Cardiovascular Outcomes in Patients With Chronic Coronary Syndrome Treated With Colchicine
Authors: Niekbachsh Mohammadnia, Amber van Broekhoven, Willem A Bax, John W Eikelboom, Arend Mosterd, Xiaohong Yang, Jan G Tijssen, Peter L Thompson, Dominique de Kleijn, Saloua El Messaoudi, Sotirios Tsimikas, Calvin Yeang, Jan H Cornel
Journal: Circulation (2023)

Introduction: Lipoproteins carrying pro-inflammatory oxidized phospholipids (OxPL), exemplified by lipoprotein(a) [Lp(a)], contribute to residual risk for major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS) despite optimal medical treatment. Hypothesis: Anti-inflammatory colchicine therapy modifies MACE in patients with elevated Lp(a), OxPL on apo(a) [OxPL-apo(a)], and OxPL on apoB containing lipoproteins (OxPL-apoB). Aims To study the relationship of Lp(a), OxPL-apo(a) and OxPL-apoB with MACE in 1777 LoDoCo2 trial participants with CCS randomized to colchicine or placebo. Methods: End of study but not baseline samples were available. Because Lp(a), OxPL-apo(a) and OxPL-apoB levels are strongly genetically determined, we assumed that end of study values would reflect baseline values. The primary endpoint was a composite of MI, ischemic CVA or ischemia driven coronary revascularization. Cox regression was used to compare the incidence of the primary endpoint by Lp(a) dichotomized at 125 nmol/L and OxPL-apo(a) and OxPL-apoB in tertiles. Results: At study end, median (IQR) on-colchicine Lp(a), OxPL-apo(a), and OxPL-apoB levels in nmol/L were 22.4 (7.2-102.7), 7.8 (2.0-34.5) and 3.1 (1.3-6.3), similar to on-placebo levels of 23.9 (9.9-95.7), 8.8 (2.7-34.0), and 3.1 (1.4-5.9), respectively (p = 0.20, 0.98 and 0.18). MACE reduction with colchicine was independent of Lp(a) and OxPL-apo(a) (P interaction = 0.92 and 0.66 respectively). However, the largest MACE reduction was present in the highest vs lowest OxPL-apoB tertile ( Figure , P interaction &lt; 0.05). Conclusions: The benefit of colchicine in reducing MACE was highest in subjects with elevated OxPL-apoB, suggesting colchicine may be most effective in subjects with heightened oxidation-driven inflammation. These findings may be hypothesis-generating and require validation in larger trials with baseline biomarker assessment including CRP and IL-6.
Abstract 14517: apoE Receptor-2-R952Q Variant in Macrophages Potentiates Hyperlipidemia and Atherosclerosis in LDL Receptor-Knockout Mice via Increased Secretion of Soluble LDL Receptor-Related Protein-1
Authors: Vanessa M Turkson, April Haller, Anja Jaeschke, David Y Hui
Journal: Circulation (2023)

Introduction and objective: Apolipoprotein E Receptor-2 (apoER2) is a type I transmembrane receptor in the LDLR family expressed in vascular smooth muscle cells (VSMC), endothelium, and macrophages. An apoER2 mutation referred to as apoER2-R952Q (R952Q) is associated with elevated plasma triglyceride levels and increased risk of premature coronary artery disease and myocardial infarction in humans. This study investigated the role of the R952Q mutation of apoER2 in modulating disease development. Methods and Results: We generated R952Q-expressing mice using a CRISPR-directed approach. This mouse line was crossed with the LDLR knockout mouse line and the progenies were fed a high cholesterol diet for 16 or 24 weeks. Results showed that unlike apoER2 knockout, the accelerated atherosclerosis R952Q variant mice exhibited was linked to increased plasma lipid levels. Considering apoER2's expression, which is notably absent in hepatocytes, we investigated the impact of R952Q myeloid cells on disease progression via bone marrow transplant. Results showed that wildtype apoER2 mouse recipients of R952Q bone marrow recapitulated the elevated plasma lipid level phenotype while R952Q mouse recipients of wildtype apoER2 bone marrow did not. Due to the absence of LDLR in our model, we investigated LRP1’s role in the context of myeloid-specific R952Q and found an increase in the production of hypercholesterolemia-associated soluble LRP1 (sLRP1) in the plasma of high cholesterol diet-fed mice with myeloid-specific R952Q. sLRP1 may compete with cell-surface LRP1 in lipoprotein clearance, suggesting a novel mechanism by which the R952Q mutation in macrophages may increase plasma lipid levels, thereby accelerating atherosclerosis. Conclusion: The R952Q mutation in apoER2 accelerates atherosclerosis via overproduction of soluble LRP1, a gain-of-function mechanism in macrophages resulting in hypercholesterolemia.
Abstract 14634: Hybrid vs. Norwood: Analysis of the NPC-QIC Database to Determine Optimal Approach for High-Risk Single Ventricle Patients
Authors: Connor P Callahan, Paighton Miller, Horacio Carvajal, Matthew Canter, Chelsea Mannie, Fei Wan, Garick D Hill, Pirooz Eghtesady
Journal: Circulation (2023)

Background: Infants w/ high risk hypoplastic left heart syndrome and variants (HR-HLHS) due to low birth weight or gestational age experience worse outcomes. Optimal management remains unknown. We sought to 1. compare primary Norwood to hybrid strategies in HR-HLHS 2. identify predictors of futility. Hypothesis: Primary Norwood offers improved outcomes compared to hybrid strategies. Very low birth weight and other anomalies may represent futility. Methods: We reviewed HR-HLHS from the National Pediatric Cardiology Quality Improvement Collaborative database. Patients with birth weight &lt;2.5kg or gestation &lt;35 weeks, and age ≤ 30 days at admission were included (N=398). Norwood (n=225), hybrid (pulmonary artery band (PAB) + ductal stent, n=76), and PAB w/ prostaglandin (PAB/PGE, n=77) were compared. Transplantation referral (n=1) and comfort care (n=19) occurred. Baseline factors, 1-year survival, and stage 2 completion were reviewed. Results: Table shows baseline HR-HLHS features. Norwood had higher risk adjusted 1-year survival and stage 2 completion than hybrid strategies, including in &lt; 2.1 kg (Figure). On multivariable analysis, hybrid (HR 2.8), genetic abnormality (HR 1.5), and ECMO (HR: 7.2) were significantly associated w/ decreased 1-year survival and stage 2 completion, while higher birth weight (HR: 1.5) was associated w/ increased stage 2 completion. Less than 25% of HR-HLHS w/ birthweight &lt; 2.1 kg and ≥ 1 genetic abnormality was alive with stage 2 at the end of follow-up. Conclusions: HR-HLHS have better outcomes following primary Norwood than hybrid palliation. In patients w/ birth weight &lt; 2.1 kg and genetic abnormalities, hybrid or Norwood may be futile.