tbuckley/cabot-search huggingface dataset:
Abstract 4141578: Clinical Determinants and Prognostic Significance of Angiopoietin-like Protein 3 in Patients with Cardiovascular Disease
Authors: Hiroki Tanaka, Yunosuke Matsuura, Kohei Moribayashi, Kinuko Yamamoto, Soichi Komaki, Masashi Yamaguchi, Takeshi Ideguchi, Koichi Kaikita
Journal: Circulation (2024)

Background: Angiopoietin-like protein 3 (ANGPTL3) has garnered attention as a target for managing clinical lipid profiles. However, the determinants of blood ANGPTL3 levels and their prognostic significance in cardiovascular disease (CVD) remain unclear. Aims: This study aimed to investigate the clinical determinants and prognostic significance of serum ANGPTL3 levels in patients with CVD. Methods: A total of 311 patients with CVD (mean age 71 years, 61% male, mean body mass index 24 kg/m 2 , 42% diabetic, median estimated glomerular filtration rate (eGFR) 57 mL/min/1.73 m 2 , 152 patients with ischemic heart disease, 75 with valvular heart disease, 30 with cardiomyopathy, 54 with other CVD) were enrolled. Serum ANGPTL3 levels were measured using an enzyme-linked immunosorbent assay (R&amp;D Systems) and analyzed for associations with clinical characteristics and the incidence of major adverse cardiovascular events (MACE), including all-cause mortality, non-fatal myocardial infarction, heart failure hospitalization, and ischemic stroke during a one-year follow-up. Results: Serum ANGPTL3 levels were significantly higher in females than in males (92 [78-112] vs. 74 [56-94] ng/mL, p &lt; 0.0001). These levels showed positive correlations with age and the levels of CRP and BNP, while negative correlations were observed with eGFR, total bilirubin (T-bil), alanine aminotransferase (ALT), albumin (Alb), hemoglobin (Hb), and platelet counts. No association was found with lipid profiles or specific CVD etiologies. Multivariate analysis identified gender, CRP, eGFR, ALT, and Hb levels as independent determinants of serum ANGPTL3 levels. During the follow-up period, 30 patients developed cardiovascular events, and receiver operating characteristic curve analysis identified a serum ANGPTL3 cutoff of 90.7 ng/mL for optimal event discrimination. Kaplan-Meier analysis showed a significantly higher incidence of MACE in patients with ANGPTL3 levels above the cutoff than those below (log-rank test, p = 0.0013). Multivariate Cox regression analysis identified elevated ANGPTL3 level as an independent determinant of MACE (hazard ratio: 1.01; 95% confidence interval: 1.00-1.02; p = 0.018). Conclusions: In patients with CVD, serum ANGPTL3 levels, determined by gender, inflammation, liver and renal function, and anemia, can discriminate populations at high risk of developing future cardiovascular events.
Abstract 4140912: Patient Demographics and Appropriateness of Elective Percutaneous Coronary Intervention in a Brazilian Cardiology Center
Authors: Sara Del Vecchio Ziotti, Thiago Pereira, sarah grobe, Carlos Serrano, LUIZ CESAR, Alexandre Abizaid, Luis Henrique Gowdak
Journal: Circulation (2024)

Background: The “Appropriate Use Criteria for Coronary Revascularization” guide clinicians in delivering high-quality care and optimizing medical resource utilization. While previous studies have indicated an approximately 10% rate of inappropriateness of non-acute percutaneous coronary interventions (PCI), there is a lack of similar data in Brazil. Research Question: This study sought to determine the rate of appropriate elective PCI at a cardiology reference hospital in Brazil. Goals: The primary goal was to ascertain the frequency of elective PCI categorized as appropriate, potentially or rarely appropriate. The secondary objective aimed to identify patient characteristics associated with PCI inappropriateness. Methods: In this retrospective study, we included stable patients with chronic coronary syndromes (CCS) who underwent elective PCI between 2017 and 2020 at a cardiology hospital in Sao Paulo, Brazil. The appropriateness of the PCI was assessed using the ACC/AHA criteria proposed in 2017. The adequacy of the procedure was assessed at the “territory level” of the coronary arteries (left main [LM], left anterior descending [LAD], circumflex [CX], and right coronary artery [RCA]). Clinical variables associated with rarely appropriate PCI were identified from the cohort of patients with single-vessel procedure. Results: 467 patients underwent 474 elective PCI with 543 treated coronary territories. We classified 59 (10.9%), 263 (48.4%), and 221 (40.7%) PCI as rarely appropriate, possibly appropriate, and appropriate, respectively. Single-vessel PCI was found in 332 patients. Factors associated with an increased rate of rarely appropriate were male (OR 2.83, 95% CI 1.14-7.02), no symptoms (OR 8.24, 95% CI 3.79-17.91), and having a positive functional test (OR 13.12, 95% CI 3.94-43.72). Factors associated with a decreased rate of rarely appropriate were depending on the public health system (OR 0.20, 95% CI 0.095-0.43), previous myocardial infarction (OR 0.21, 95% CI 0.07-0.6), previous PCI (OR 0.22, 95% CI 0.08-0.63), and current use of beta-blockers (OR 0.24, 95% CI 0.12-0.49). Conclusion: Rarely appropriate PCI was more prevalent among asymptomatic men with no previous myocardial infarction, not adequately medicated, and having a private health plan. These findings suggest a possible overuse of elective PCI in those patients, prompting health care providers to carefully review the indications of a costly, potentially risky procedure such as PCI.
Abstract 4141516: Cross-species single-cell RNA sequencing reveals divergent phenotypes and activation states of adaptive immunity in human carotid and experimental murine atherosclerosis
Authors: Hauke Horstmann, Nathaly Anto-Michel, Xia Sheng, Holger Winkels, Ingo Hilgendorf, Teresa Gerhardt, Alma Zernecke, Peter Kohl, Amanda Foks, Dirk Westermann, Andreas Zirlik, Dennis Wolf
Journal: Circulation (2024)

Background and Aims: The distinct functions of immune cells in atherosclerosis have been mostly defined by preclinical mouse studies. Contrastingly, the immune cell composition of human atherosclerotic plaques and their contribution to disease progression is only poorly understood. It remains uncertain whether genetic animal models allow for valuable translational approaches. Methods and Results: Single cell RNA-sequencing (scRNA-seq) was performed to define the immune cell landscape in human carotid atherosclerotic plaques. The human immune cell repertoire demonstrated an unexpectedly high heterogeneity and was dominated by cells of the T-cell lineage, a finding confirmed by immunohistochemistry. Bioinformatical integration with 7 mouse scRNA-seq data sets from adventitial and atherosclerotic vascular tissue revealed a total of 51 identities of cell types and differentiation states, of which some were only poorly conserved between species and exclusively found in humans. Locations, frequencies, and transcriptional programs of immune cells in mouse models did not resemble the immune cell landscape in human carotid atherosclerosis. In contrast to standard mouse models of atherosclerosis, human plaque leukocytes were dominated by several T-cell phenotypes with transcriptional hallmarks of T-cell activation and memory formation, T-cell receptor-, and pro-inflammatory signaling. Only mice at the age of 22 months partially resembled the activated T-cell phenotype. In a validation cohort of 43 patients undergoing carotid endarterectomy, the abundance of activated immune cell subsets in the plaque defined by multi-color flow cytometry associated with the extend of clinical atherosclerosis. Conclusions: Integrative scRNA-seq reveals a substantial difference in the immune cell composition of murine and human carotid atherosclerosis – a finding that questions the translational value of standard mouse models for adaptive immune cell studies. Clinical associations suggest a specific role for T-cell driven (auto-) immunity in human plaque formation and -instability.
Abstract 4141280: Machine Learning Predicts 24-Hour Change in Decongestion Biomarkers in Hospitalized Heart Failure Patients
Authors: Arash Harzand, Dmytro Vremenko, Alexander Wilcox, Claire Beskin, Ruizhi Liao, Jacob Joseph
Journal: Circulation (2024)

Background: Despite recent advances, patients with heart failure (HF) often experience repeat hospitalizations and worsening clinical trajectories from inadequate decongestion. Evidence-based approaches for optimizing interventions in the acute hospital setting for patients with decompensated HF are needed. We evaluated whether machine learning (ML) models can accurately predict next-day levels for decongestion surrogates in hospitalized HF patients. Hypothesis: ML can accurately predict body weight, hematocrit, creatinine, and potassium values in the next 24 hours in hospitalized HF patients. Methods: We utilized national Veterans Affairs (VA) databases to study all patients admitted with HF from January 2014 to July 2022. Records including at least one value for at least one biomarker of interest (body weight, hematocrit, creatinine, and potassium) were included. Patients were randomly split into training (80%), validation (10%), and test (10%) datasets. We trained a recurrent neural network to predict each biomarker’s value on admission day n+1 using data until day n, simulating a scenario where a clinician monitors response to treatment (e.g., diuresis) over a 24-hour cycle. The model that performed best on the validation set was evaluated on the test set. The R 2 , mean absolute error (MAE), and feature importance were determined. Results: We identified 589,114 admissions involving 124,163 unique patients. The mean (SD) age on admission was 72 (10) years; 98% were male, 69% were white, and 25% were Black. The performance (R 2 , MAE) for each biomarker model was as follows: body weight (0.94, 6.15 lb.), creatinine (0.92, 0.21 mg/dL), hematocrit (0.86, 1.7%), and potassium (0.53, 0.27 mmol/L). The top predictive features across all models were intravenous or oral diuretic use, patient age, and diastolic blood pressure. The predicted 24-hour change in each biomarker based on total daily diuretic dose for five representative patients is demonstrated in the Figure. Conclusions: ML can accurately predict the 24-hour body weight, hematocrit, creatinine, and potassium values in hospitalized HF patients, suggesting the potential for AI to guide acute in-hospital management.
Abstract 4141168: CD 34+ Cell Therapy is Associated With Improved Myocardial Perfusion in Heart Failure With Preserved Ejection Fraction
Authors: Gregor Poglajen, Rok Zbačnik, Sabina Frljak, Gregor Zemljic, Andraz Cerar, Bojan Vrtovec
Journal: Circulation (2024)

Background: In HFpEF patients transendocardial CD34+ cell therapy was shown to improve systolic and diastolic properties of the myocardium. However, the underlying mechanisms remain poorly defined. Aim: As coronary microvascular dysfunction is thought to represent a central pathophysiological mechanism of HFpEF, we sought to evaluate the potential correlation between CD34+ cell therapy and myocardial perfusion in HFpEF patients. Methods: We performed a cardiac MRI (cMRI)-based subanalysis of a prospective pilot study that investigated clinical effects of transendocardial CD34+ cell therapy in HFpEF patients. All patients underwent transendocardial autologous CD34+ cell transplantation using electroanatomical mapping system targeting areas of local mechanical diastolic delay &gt;50 ms. At baseline and 6 months we performed clinical, biochemical, echocardiographic and cMRI evaluation. A 17-segment model was used for cMRI segmental perfusion analysis, which was assessed using gadolinium contrast and a first pass perfusion approach. We analyzed segmental myocardial perfusion using cMRI segmental perfusion data normalized to baseline blood pool (BP) AUC for each patient. Results: Of 12 patients 2 (17%) were female and the average age was 68±6 years. 6 (100%) patients had a history of hypertension, 2 (17%) had diabetes and 3 (33%) had hyperlipidemia. We found no differences between baseline and follow-up in creatinine (99±28 μmol/L vs. 100±29 μmol/L; P=0.91), bilirubin (18±10 mmol/L vs. 15±5 mmol/L; P=0.33), and NT-proBNP (1581±1079 pg/mL vs. 1437±902 pg/mL; P=0.74) serum levels. Left ventricular systolic function also remained unchanged (LVEF; 62±8% vs. 63±8%; P=0.75 and GLS;-13.3±1.9% vs. -13.5±2.4%; P=0.86). However, left ventricular diastolic function significantly improved at 6 months (E/e'; 17.6±3.6 vs. 12.5±2.0; P=0.002). When performing myocardial segmental analysis, we found significantly higher myocardial viability in injected (N=54) than in noninjected (N=45) electroanatomical segments (15.3±3.8 mV vs. 11.3±4.5 mV; P=0.00001). Moreover, at 6 months myocardial perfusion was significantly improved in 89 injected corresponding cMRI segments, but it remained unchanged in 103 noninjected segments (111±44% vs. 97±21%; P=0.004). Conclusion: In HFpEF patients, CD34+ cell therapy may be associated with an increase in myocardial perfusion of the target myocardium, which may result in beneficial echocardiographic and clinical benefits observed in this patient cohort.
Abstract 4140880: Clinical Hepatic Scores as Predictors of Major Adverse Cardiovascular Events in a SMuRFless Population
Authors: Pamela Alebna, Mathew Ambrosio, Blessan Sebastian, Gabrielle Bolden, Divine Akakpo, Nicholas Chew, Anurag Mehta
Journal: Circulation (2024)

Background: Recent evidence suggests that a significant proportion of individuals presenting with myocardial infarction lack standard modifiable cardiovascular disease risk factors (SMuRFs). This SMuRFless population has an elevated risk of mortality, highlighting the need for identifying novel risk markers. Liver steatosis and fibrosis are potential non-traditional markers that have not been evaluated in this population. Therefore, this study investigates clinical hepatic scores as proxies for metabolic liver disease and their association with major adverse cardiovascular events (MACE) in a SMuRFless population within the UK Biobank. Methods: We analyzed data from the UK Biobank, a population-based cohort study with a median follow-up of 11 years. The Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), and Fibrosis Index Based on 4 Factors (FIB-4) were used as non-invasive measures to predict metabolic dysfunction-associated steatotic liver disease, hepatic steatosis, and hepatic fibrosis, respectively. Participants with hypertension, hyperlipidemia, diabetes, or cigarette smoking (SMuRFs) were excluded. Cox proportional hazards models were used to assess the association between FLI, HSI, and FIB-4 scores and MACE, defined as fatal and non-fatal myocardial infarction, stroke, and peripheral artery disease. Results: Among 81,339 SMuRFless participants, the mean age was 51.5 years (SD 7.9), and 50,347 (62%) were women. In unadjusted models, higher liver scores (FLI, HSI, and FIB-4) were significantly associated with MACE. Participants with FLI &gt; 60 had a hazard ratio (HR) of 2.01 (95% CI: 1.68-2.41) compared to those with FLI &lt; 60. Those with HSI &gt; 36 had HR of 1.38 (95% CI: 1.14-1.54) compared to HSI &lt; 36, and participants with FIB-4 &gt; 2.67 had an HR of 4.17 (95% CI: 3.27-5.31) compared to FIB-4 &lt; 1.3. However, after adjusting for age, race, hemoglobin A1C, triglycerides, LDL-cholesterol, total cholesterol, body mass index (BMI), and creatinine, these associations were attenuated, and HRs were not statistically significant (Table). Conclusion: FLI, HSI, and FIB-4 scores are not significant predictors of MACE in a SMuRFless asymptomatic population after adjusting for confounders.
Abstract 4141149: Atrial remodelling drives arrhythmia in Fabry Disease
Authors: Ashwin Roy, Christopher OShea, Max Cumberland, Andrew Holmes, Davor Pavlovic, Jonathan Townend, Tarekegn Geberhiwot, Katja Gehmlich, Richard Steeds
Journal: Circulation (2024)

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a-galactosidase deficiency, resulting in multi-organ accumulation of sphingolipid, namely globotriaosylceramide (Gb3). Gb3 accumulation triggers left ventricular hypertrophy, fibrosis, and inflammation, forming an environment for arrhythmia and sudden death, a common cause of FD mortality. Atrial fibrillation is common in FD and contributes to the high burden of stroke, yet the cellular mechanisms accounting for this are unknown. To address this, we conducted signal-averaged electrocardiography (ECG) analysis from a large cohort of adults with FD at varying stages of cardiomyopathy. Findings were compared with a novel human atrial model of FD, developed using gene-edited stem-cell derived atrial cardiomyocytes, exploring their molecular and functional properties. Methods: In 115 adults with FD, staged according to degree of cardiomyopathy, ECG P-wave characteristics were compared with non-FD age/sex-matched controls. Induced pluripotent stem cells were then genome-edited using CRISPR-Cas9 to carry the GLA p. N215S variant, the most common cardiac variant of FD in the UK, and differentiated into atrial cardiomyocytes (iPSC-CMs). Contraction, calcium handling and single-cell electrophysiology experiments were conducted to explore proarrhythmic mechanisms. Results: ECG analysis demonstrated P-wave duration and PQ interval shortening in FD adults with no cardiomyopathy compared with non-FD controls, which prolonged with cardiomyopathy stage. FD patients exhibited atrial dilation, high incidence of premature atrial contractions and increased risk of AF. In our cellular model, GLA p. N215S iPSC-CMs were deficient in a-Gal A and exhibited Gb3 accumulation. GLA p. N215S iPSC-CMs demonstrated a more positive diastolic membrane potential, a faster action potential upstroke velocity, a greater burden of delayed afterdepolarizations, greater contraction force, slower beat rate and significant dysfunction in calcium handling compared to WT iPSC-CMs. The identified ECG changes may be partly explained by our observed cellular changes. Conclusions: These findings enhance our understanding of atrial myopathy in FD by providing novel insights into underpinning mechanisms for atrial arrhythmia as well as rationale for early identified P-wave changes in FD. Mechanisms identified in this study may be targeted in future research to develop therapeutic strategies to reduce the atrial arrhythmic burden in FD.
Abstract 4141403: Age-, Sex- and/or Ethnic- specific disparities; Biventricular systolic and diastolic strain, and biomarker, prognostic implications in Acute Tuberculous Pericarditis.
Authors: Mamotabo Matshela
Journal: Circulation (2024)

Background: Two-dimensional speckle tracking echocardiographic (2D-STE) strain analysis is modern and inovatively useful in overcoming technical echocardiographic limitations. To-date no larger studies have assessed sub-clinical myocardial mechanics in acute tuberculous pericarditis (ATBP) and age/sex/ethnic differences, and synergistic-prognostic association of these parameters with patients' outcomes (survival). Aim: To assess the prognostic relation between age/sex/ethnitic differences with right (RV) and left (LV) ventricular systolic and diastolic strain (and other parameters/biomarkers) with outcome ATBP and preserved LV function. Methods and results: A total of 362 (mean age 37years, LVEF 56%, 57% males) consecutive patients with ATBP were enrolled and subseguently had 2D-STE strain analysis performed on their the 2D-TTE images. Sex, age and ethnic differences were assessd and all were prospectively followed for new CVS events including new onset acute heart failure or deterioration in LV function, hospitalization for HF, CVS-related death, recurrent effusion or tamponade . The LV and RV longitudinal strain parameters were assessed using the 2D-STE. Of the 362 patients eligible for the study, 142 developed 84 new CVS-related events during a mean follow-up of 12 ±6 months. The RV free-wall, global RV and LV systolic and diastolic strain parameters, elevated NT Pro-BNP and troponins, RV fractional area change, low TAPSE, LV end-diastolic volume, LA volume index, moderate TR, and mPASP &gt; 40mmHg were independently predictive of combined outcomes (p &lt;.0001). ATBP demonstrated impaired RV&gt;LV strain parameters and best performance predictive of CVS events was greatest for RV compared with LV strain. There was a stronger association between the degree of RV dysfunction and risk of CVS events for RV free wall- and global systolic and diastolic strain parameters and biomarker compared with LV strain parameters. Male sex, older age (at least 42years) and black etnicity were further independent risk factors of outcomes. Conclusion: Patients with ATBP and normal LVEF, and myocardial mechanical dysfunction in addition to elevated biomarkers were stronger predictors of outcome more so for those with RV dysfuntion than other conventional and LV mechanical parameters. Male sex, older age and black ethnicity provided additional independent risk of outcomes in ATBP, providing stronger prognostic stratification.
Abstract 4141131: Pathophysiological evidence for abnormal P-wave terminal force reflects atrial myopathy
Authors: Juntae Kim, Daehoon Kim, Oh-Seok Kwon, Hee Tae Yu, Tae-Hoon Kim, Jae-Sun Uhm, BOYOUNG JOUNG, Moon-Hyoung Lee, Hui-Nam Pak
Journal: Circulation (2024)

Background: Although P-wave terminal force (PWTF), a marker of atrial myopathy, has been implicated in predicting incident atrial fibrillation (AF) and ischemic stroke, its pathophysiological mechanisms remain unclear. This study investigates the association between abnormal PWTF and atrial myopathy, diastolic function, epicardial adipose tissue (EAT), or AF recurrence following AF catheter ablation (AFCA). Methods: We included 3,528 AF patients (59.7 (10.8) years, 28.8% female, 64.2% paroxysmal AF) who underwent AFCA with baseline and 1-year follow-up echocardiograms. We evaluated the characteristics of the patients with abnormal PWTF (≥4000 μV × ms) and its association with clinical, hemodynamical, and imaging parameters. Result: Patients with AF and abnormal PWTF (≥4000 μV × ms) were older (p=0.001) and had higher proportions of male (p&lt;0.001) and non-paroxysmal AF (p&lt;0.001), higher CHA 2 DS 2 -VASc (p=0.011), H 2 FPEF scores (p=0.003), higher left atrial (LA) dimension (p&lt;0.001), left ventricular mass index (p=0.001), LA pressure (n=3,067, p=0.014), and atrial EAT volume (p&lt;0.001), and lower LA strain (n=368, p=0.036) than their counterpart. The patients with abnormal PWTF were independently associated with age (OR 1.01 [1.00-1.02], p=0.007), male gender (OR 1.64 [1.33-2.01], p&lt;0.001), non-paroxysmal AF (OR 1.37 [1.14-1.66], p=0.001), LA volume index (OR 1.02 [1.01-1.03], p&lt;0.001), or atrial EAT volume (OR 1.00 [1.00-1.01], p=0.028). Among 2,929 patients who did not recur within a year, PWTF was an independent predictor of blunted LA reverse remodeling a year after AFCA (OR 0.97 [0.94-0.99], p=0.029). During a median follow-up of 31 (interquartile range 15–61) month, patients with abnormal PWTF demonstrated a significantly higher AF recurrence (log-rank p=0.010; HR 1.14 [1.04-1.25], p=0.008). Conclusion: Abnormal PWTF is associated with a blunted LA reverse remodeling, atrial EAT volume, and an increased risk of AF recurrence following catheter ablation and is indicative of LA myopathy.