tbuckley/cabot-search huggingface dataset:
Abstract 15739: Fetal Echocardiographic Predictors of Perinatal Outcome in Congenital Atrioventricular Block
Authors: Nina A Conn, Stuart Lipsitz, Lynn A Sleeper, Wayne Tworetzky, Laura Gellis, David N Schidlow, Kevin G Friedman
Journal: Circulation (2023)

Background: Congenital atrioventricular block (AVB) is a rare disease with poor outcomes. Heart rate (HR) is a major prognostic factor. To date, no study has evaluated the contribution of cardiac output (CO), stroke volume (SV), and HR on outcomes. Methods: In this retrospective study we evaluated associations between fetal echocardiographic parameters and risk of a composite severe fetal adverse event (AE) in patients with congenital AVB. Results: Of the 58 cases of congenital AVB, 21 (36%) had the composite AE, defined as fetal hydrops (8/58, 14%), ≥ moderate ventricular dysfunction (LV 3/58, 5%; RV 6/58 11%), fetal demise (2/57, 4%), or premature birth at ≤ 35 weeks (17/55, 31%). Of the 55 live births, 3/55 (5%) patients died and 35/55 (64%) had a pacemaker placed in the neonatal period. In univariate analysis, lower HR z-score was associated with the composite AE (p = 0.002) and all individual components of the composite AE. Higher LV end diastolic volume was associated with the composite AE (p = 0.004), premature birth (p = 0.006) and neonatal pacemaker placement (p = 0.009). Higher LV SV was associated with the composite AE (p = 0.003) and with fetal hydrops (p = 0.031) and premature birth (p = 0.002). Higher combined CO (p = 0.038), presence of structural heart defect (p = 0.038) and heterotaxy (p = 0.01) were associated with fetal hydrops. In multivariate analysis, lower HR z-score (p = 0.044) and higher LV SV (p = 0.037) were associated with the composite AE. Longitudinal analysis showed the AE group had lower HR and higher SV throughout gestation and trends towards a greater decline in SV and CO (particularly RV CO) in the third trimester. Conclusions: Heart rate, not CCO, is the primary determinant of perinatal outcome in fetuses with high grade AVB. The compensatory increase in LV volume and SV in the patients with the lowest HR (and worst outcomes) maintains CCO in most fetuses with AVB and reflects the ability for fetal cardiac adaptation in the setting of prolonged severe bradycardia.
Abstract 18338: TBX4 Loss-of-Function Within the Embryonic Lung Mesenchyme Disrupts Postnatal Lung Development and Increases Susceptibility to Pulmonary Hypertension
Authors: Gabriel Maldonado Velez, Todd Cook, Micheala A Aldred
Journal: Circulation (2023)

Introduction: The T-box 4 (TBX4) transcription factor is recognized as a risk gene in pulmonary arterial hypertension (PAH). TBX4 is expressed within the lung mesenchyme in the developing lung and is required for lung branching morphogenesis. Genetic studies report that PAH cases with TBX4 mutations display an earlier onset of the disease. In addition, studies have reported carriers of TBX4 mutations with diffused alveolar development and pulmonary hypertension (PH). Currently, there is a lack of evidence on the effect of TBX4 loss-of-function (LoF) on later stages of lung development and predisposition to lung disease. Hypothesis: Lung mesenchyme Tbx4 deletion within the developing lung disrupts essential gene regulatory networks leading to abnormal postnatal lung development and susceptibility to pulmonary hypertension. Methods: We have generated Tbx4 conditional knockout ( Tbx4-CKO ) mice in which Cre recombinase removes the exon 5 of Tbx4 within the embryonic lung mesenchyme, creating a null allele. To examine alveolarization, we harvested postnatal day 14 (P14) and 36 (P36) lungs and calculated mean linear intercept (MLI). RNA-seq was performed at both stages to identify disrupted gene networks in Tbx4-CKO lungs. RVSP was measured by right heart catheterization in six-month-old mice to evaluate for PH. Results: Tbx4-CKO lungs show increasing alveolar simplification at P14 and P36, as confirmed by increases in MLI of 24.8% and 34.4%, respectively. Tbx4-CKO mice show a statistically significant increase of 10.4% in RVSP, and preliminary analysis of vessel wall thickness suggests mild vascular remodeling in their lungs. RNA-seq analysis shows enrichment of pathways (canonical WNT, VEGF, and BMP signaling) and genes ( Lgr5 , Tnc , Wnt3a , Areg , Gdf2 , and Bmper ) relevant to lung alveologenesis, angiogenesis, and PH. Conclusions: TBX4 LoF affects lung alveolar development, similar to observations made in human cases with TBX4 mutations. The clinical presentation of such cases is broad, but our mice show features of bronchopulmonary dysplasia, including alveolar simplification and PH. Further analysis of our RNA-seq data and planned single-cell analyses should provide insight into the role of TBX4 in alveolarization and PH risk.
Abstract 18281: Identifying Predictors of ICU Mortality Outcomes Among Critically Ill Patients With Atrial Fibrillation Using Machine Learning Models
Authors: Vijval Rajan, Yanjia Zhang, Zhenwei Zhang, Md Ashfaq Ahmed, Mukesh Roy, Venkataraghavan Ramamoorthy, Muni Rubens, Anshul Saxena
Journal: Circulation (2023)

Introduction: New onset atrial fibrillation (Afib) is a frequent complication of intensive care admission and is linked to higher mortality in the ICU. We aimed to develop machine learning (ML) models to predict the risk of death in the ICU among these patients and assess their long-term prognosis. Methods: Eligible patients with Afib from the Medical Information Mart for Intensive Care IV database were included. The cases were randomly divided into training (75%) and test (25%) groups. Machine learning algorithms such as light GBM, random forest, gradient boosted classifier, and XGBoost were used. In addition, we utilized a tabular deep learning model architecture comprised of an embedding layer for categorical variables. The robustness of the results was ensured through K-fold cross-validation. AUROC and accuracy were used to compare model performance. Models accounted for variables from demographics, labs, charting events, and comorbidity domains. A web-based calculator was also developed to encourage the model's practical application. Results: The sample (n = 8455) consisted of 3408 females (40.3%), 6004 whites (71.0%), and 4876 (57.7%) patients with Medicare insurance. The ICU mortality was 9.5% (n = 802). The median age (79 vs. 75 years; p &lt; 0.001) and ICU LOS (4 vs. 2 days; p &lt; 0.001) were higher among the patients who expired. Congestive heart failure was reported in 15% of cases. The lightGBM model (AUROC: 84%) performed best and showed that mean arterial BP, WBC, PO2, platelet count, age, hemoglobin, BUN, pH, ICU LOS and anion gap were the top predictors of ICU mortality among this population. Conclusion: Death in the ICU among patients with Afib was associated with several clinical features, especially BP, WBC count, PO2, platelet count, age, and hemoglobin. Predictors of ICU mortality were identified with high accuracy and this may aid in the creation of a real time risk score for selective intervention to reduce the risk of death in this vulnerable patient population.
Abstract 13530: Life Quality, Work and Functional Recovery of Cardiac Arrest Survivors After Hospital Discharge
Authors: Kuan-Ting Lu, Yi-Wen Wu, Tai-Yuan Chen, HSIN YU LEE, Wen-chu Chiang, Matthew Ma, Min-Shan Tsai
Journal: Circulation (2023)

Background: Along with the improvement in resuscitation science and post-cardiac arrest care, an increasing number of cardiac arrest (CA) victims survived to hospital discharge. Research Questions: Do cardiac arrest survivors return to their life and work after hospital discharge? Aims: To investigate whether the life quality, work ability, and neurological recovery of cardiac arrest survivors improves continuously within 1 year after hospital discharge. Methods: The retrospective single center study enrolled 169 non-traumatic adult CA patients who survived to hospital discharge between 2017 and 2020. The following were excluded: patients who expired within 1 year following hospital discharge, patients who unable to be contact after hospital discharge, and patients who refused to join the study. A total of 71 patients were included in this study. The use of medical service including outpatient and ER visit, and hospital admission were collected from medical record. The work status, life quality and neurological function were evaluated by questionnaires including the World Health Organisation Quality of Life Brief Form and EuroQol 5-Dimension, 5-Level Health Scale (EQ-5D-5L). Results: There were 67 patients (94.4%) discharged with cerebral performance category (CPC) of 1, and the 2 patients (2.8%) with CPC of 2. Most patients (64, 90.1%) returned home. Sixty-seven patients (94.4%) returned to outpatient visit at a median time of 6 days, 22 patients (31%) visited ER at a median time of 70 days, and 21 patients (29.6%) were hospitalised again at a median time of 44 days. The neurological function evaluated by CPC at 3 months and 1 year post-discharge did not show significant improvement. Patients demonstrated improved ability to work as well as improved scores for overall life quality, general health, physical, psychological, social relations, and environmental status. With regard to mobility, self-care, usual activities, pain/discomfort, and health state assessed by EQ-5D-5L, the patients with more than moderate impaired also decreased significantly. Conclusions: Life quality and work ability of CA survivors improved continuously within 1 year after hospital discharge.
Abstract 14250: ND-13, a Small DJ-1 Derived Peptide, Confers Cardioprotection by Targeting Mitochondrial Homeostasis
Authors: Aishwarya Prakash, Sze Jie Loo, Fan Yu, Shuo Cong, Siavash Beikoghli Kalkhoran, Gustavo Enrique Crespo Avilan, Dani Offen, Chrishan Ramachandra, Sauri Hernandez Resendiz, Derek Hausenloy
Journal: Circulation (2023)

Objectives: DJ-1 protein is a multifunctional protein with cardioprotective effects against acute myocardial ischemia-reperfusion injury (IRI). This study aims to elucidate whether ND-13, a small peptide derived from DJ-1, can confer acute cardioprotection after IRI by preserving mitochondrial homeostasis through improvements in mitochondrial respiratory capacity and regulating the balance between mitochondrial fusion/fission. By enhancing mitochondrial respiration and maintaining the integrity of the mitochondrial network, ND-13 may provide a novel therapeutic strategy for cardioprotection in cardiomyocytes following IRI. Methods: In vitro , ex vivo and in vivo murine models of IRI were used to elucidate the cardioprotective effects of ND-13. Infarct size, cardiac function and mitochondrial function were assessed. Results: ND-13 was shown to confer cardioprotection in three distinct models of IRI: (i) in vitro , cardiomyocyte (CM) death was reduced by 42% (64±1% untreated vs 37±2% treated; p≤0.01); (ii) ex vivo Langendorrf, with 43% decrease in infarct size (51±6.4% untreated vs 29±8.8% treated; p≤0.05); (iii) in vivo , with 35% reduction in infarct size (49±6.4% untreated vs 32±5.0% treated; p≤0.0001). CMs treated with ND-13 in the in vitro model of IRI demonstrated a significant increase in mitochondrial respiration rates, (basal: untreated 37±3 vs treated 63±10 pmol/min/cells, p≤0.05; maximal: untreated 286±20 vs treated 494±53 pmol/min/cells, p≤0.001; and spare respiratory capacity: untreated 251±18 vs treated 421±43 pmol/min/cells, p≤0.001) and a significant increase in levels of cytosolic ATP (untreated 4.0 ± 0.3 vs treated 5.6 ± 0.5 μM, p≤0.05). Conclusion: We demonstrate for the first time, cardioprotection with the DJ-1-derived peptide, ND-13, and this beneficial effect appears to be mediated by its mitoprotective actions with enhanced mitochondrial respiratory efficiency and increased ATP production. Upcoming research aims to explore if ND-13 promotes oxidative phosphorylation by directly binding to complexes of the electron transport chain to maximize respiratory function or by enhancing pyruvate dehydrogenase activity, thereby potentially influencing the regulation of the fission/fusion process.
Abstract 17170: Association of Plasma Homocysteine Levels in Cancer Survivors - Data From Framingham Heart Study Offspring Cohort
Authors: Vanessa-Rose G Turpin, Britton C Scheuermann, Carl J Ade
Journal: Circulation (2023)

Introduction: Cancer survivors experience a high prevalence of vascular remodeling from their anti-cancer therapies, which can lead to arterial stiffness. High plasma homocysteine (Hcy) is associated with increased cardiovascular disease risk via its role in decreasing nitric oxide bioavailability and impairing vascular function. However, there is limited work on its role in cancer survivorship. We, therefore, hypothesized that survivors of breast, gastrointestinal, and prostate cancer with elevated plasma Hcy values have higher arterial stiffness and lower endothelial function compared to those with low plasma Hcy. Methods: We evaluated cardiovascular disease-free cancer survivors in the Framingham Heart Study Offspring Cohort (n=196, 66±8 years old, 55.1% women, 26.4±1.2 years from cancer diagnosis, Range: [23.8 - 29.6 years]) with plasma Hcy measurements. The cohort median plasma Hcy was used to define low (&lt;8.16 μmol/L) and high Hcy (≥8.16 μmol/L) groups. Arterial stiffness was assessed via carotid-femoral pulse wave velocity (cfPWV). Peripheral vascular endothelial function was assessed via endothelium-dependent brachial artery flow-mediated dilation (FMD). Differences in cfPWV, FMD, and cardiovascular risk factors were assessed via independent sample t-test or chi-square test. Differences in cfPWV and FMD were further assessed via one-way ANCOVA with age, sex, and cardiovascular medications included as covariates. Results: cfPWV was significantly higher in the high Hcy (9.9±1.5m/s) vs. low Hcy group (8.5±1.9m/s, p=0.005); however, there were no differences in FMD between groups (2.4±1.7 vs. 2.7±2.0%, p=0.42). After controlling for our covariates, cfPWV was still significantly higher in the high Hcy group (Mean[95% CI]): (9.8[9.0-10.61]) compared to the low Hcy group (8.5[8-9.1]) (p=0.015). Conclusions: Our findings suggest an association between elevated Hcy and an increase in arterial stiffness in cancer survivors. This supports the potential adverse consequences of vascular stiffening following cancer diagnosis and treatment which could have long-term cardiovascular health implications.
Abstract 18598: Contributions of Alpha-Ketoglutarate Dependent Oncometabolism to HFpEF in Two Mouse Models
Authors: Ali Kamiar, Monique Williams, Jose Manuel Condor, Monica Anne Rasmussen, Qusai Alitter, Keith A Webster, Katarzyna Kazmierczak, Jingsheng Liang, Danuta Szczesna-Cordary, Lina A Shehadeh
Journal: Circulation (2023)

Introduction: Switching from fatty acid oxidation to less efficient but more expeditious glycolysis is associated with oncometabolism and more recently cardiac hypertrophy. Hypothesis: We hypothesized that such a switch drives HFpEF in two diverse mouse models. Methods: WT/129J mice at age 4-weeks were subjected to biweekly p407 i.p. injections and a single i.v. injection of AAV9-cTnT-LDLR. A separate group of injected mice were fed a diet supplemented with alpha-ketoglutarate (2% αKG) at onset. 4-week-old Alport mice received either αKG diet or normal chow. Glucose uptake was measured by whole-body PET-CT imaging of 18F-FDG in four groups: (1) untreated (n=5), (2) LDLR/P407 at 1, 2, 4, 7 and 8-week treatment (n=3-5), (3) LDLR/P407 + αKG mice at 4-week treatment (n=5), and (4) 9-12-week Alport mice (n=5). Echocardiography was performed on all the groups (n=4-17). Mechanical and energetic measurements on skinned cardiac pupillary muscles were performed on late-stage Alport , 8-week-treated LDLR/P407 , 4-week-treated LDR/P407 + αKG mice, and untreated controls (n=4-9). Survival of LDLR/P407, LDLR/P407/αKG and control groups (n=8-13) were recorded. Results: PET-CT scans showed increased cardiac glucose uptake in Alport (FC=3, p&lt; 0.05) and LDLR/P407 mice at 1, 2, 4 (FC = 2, p&lt;0.05), and 8 weeks (FC=3.2, p&lt;0.001). αKG diet increased cardiac glucose uptake in LDLR/P407 at 4 weeks compared to normal chow (FC=2.15, p&lt;0.05). Doppler and echocardiography showed worse diastolic dysfunction (E/E’) (FC = 1.8, P&lt;.05) in LDLR/P407 αKG mice at 4-weeks versus control chow and reduced heart size (volume) (FC = 0.41, P&lt;0.05) and worse diastolic dysfunction in Alport mice fed αKG diet. Alport hearts favored a DRX state (FC= 1.52, p &lt;.0001) while 8-week-LDLR/P407 hearts favored SRX (FC=1.1, p&lt; 0.05). The SRX state was exacerbated by αKG diet in 4-week-LDLR/P407 relative to normal chow. Life spans of LDLR/P407 mice fed αKG diet were significantly shortened (p&lt;0.001). Conclusions: The results support roles for oncometabolism in promoting HF and sudden death in Alport and LDLR/P407 mice, effects that were exacerbated by an αKG diet, and possibly caused by enhanced hypertrophic growth. The results suggest an αKGDH and phenotype-dependent redistribution of myosin energetic states
Abstract 16659: Neo LVOT Prediction With the Innovalve TMVR System - CT Preliminary Results
Authors: Orly Goitein, David Meerkin, Victor Guetta, Avi Avner, Charanjit Rihal, Ehud Raanani
Journal: Circulation (2023)

Introduction: The Innovalve TMVR is a novel self-expandable trans-catheter mitral valve prosthesis, delivered trans-septally using femoral venous access. It is deployed in an intra-valvular posterior position after sub-valvular anchoring by rotation of 6 circumferential arms. LV outflow tract (LVOT) compromise is of great concern in TMVR. A predicted Neo LVOT area of 170 mm 2 is the currently accepted cut-off for LVOT obstruction. Hypothesis: CT can accurately predict the Neo LVOT area prior to Innovalve TMVR procedure. Methods: CT was performed as a screening tool to evaluate the Neo LVOT area prior to Innovalve TMVR procedure. CT protocol: Retrospectively ECG gated with full cardiac cycle coverage. CT was performed before and after the procedure. Predicted Neo LVOT (pNLVOT) was calculated using a dedicated simulation valve prior to TMVR, actual Neo LVOT (aNLVOT) was calculated with the inserted valve in place following TMVR. The native LVOT (nLVOT) area, the predicted % LVOT reduction (nLVOT area-pNLVOT area /nLVOT area), the actual % LVOT reduction (nLVOT area-aNLVOT area /nLVOT area) and the difference between them (pNLVOT%-aNLVOT%) were calculated. Results: One hundred patients were screened for Innovalve TMVR procedure based on Neo LVOT criteria. pNLVOT≥ 170 mm 2 was found in 11 patients (11%), (7 males) average age 68±10 years, these patients underwent Innovalve TMVR procedure. The median calculated LVOT was 647.8+/-260 mm 2 (range 373-1312), the median pNLVOT reduction was 16% ±15 (range 3-53), the median aNLVOT reduction was 5%±14 (range -5-40) and the median difference between the pNLVOT and aNLVOT was 8±12 (range -4-31). In 8/11 patients (73%), the aNLVOT was larger than the pNLVOT (range difference 1 to 31%). In 3/11 patients (27%), the aNLVOT was smaller than the pNLVOT (range difference -1 to -4%). Conclusions: Underestimation of neoLVOT reduction, was uncommon and documented only minor and clinically insignificant difference between the pNLVOT and aNLVOT. As overestimation of NLVOT reduction allows a margin of safety for MTVR, we conclude that CT can serve as reliable NLVOT screening tool.
Abstract 16513: Decreased Pulmonary Blood Flow and Airway Volumes in Patients With Long COVID Syndrome Assessed by Functional Respiratory Imaging
Authors: Mariann Gyongyosi, Emilie Han, Dominika Lukovic, Eslam Samaha, Jutta K Bergler-Klein, Ena Hasimbegovic
Journal: Circulation (2023)

Introduction: In contrast to normal chest X-ray, lung computed tomography (CT), and physiological lung and cardiac functions, many patients with long COVID syndrome suffer from shortness of breath. Hypothesis: The aim of this study was to quantify the pulmonary blood and airway volumes of long COVID patients compared with that of healthy controls. Methods: Patients with long COVID syndromes were included if they had PCR-verified previous (≥3 months) SARS-CoV-2 infection, had normal laboratory (e.g. inflammation, coagulation, cardiac or other organ) parameter, normal pulmonary morphology (chest X-ray and CT) and function (spirometry and body plethysmography). The lung CT images were postprocessed by Functional Respiratory imaging analysis by using 3D reconstruction with automated lung vessel segmentation algorithm. Data of the quantitative images were compared with age, gender, and BMI-matched healthy controls. Results: Thirty patients (45±13 years, 37% male, 25.9±4.3 kg/m^2) at a median time of 256 (118-574) days after a confirmed COVID infection and 30 healthy controls (55±7y, 37% male, 26.3±2.7 kg/m^2) were included. All long COVID patients complained of dyspnoea and 14 (48.3%) patients reported thoracic pain. The total pulmonary blood volume was significantly lower in the long COVID patients compared to controls (190±24.3 mL/m^2 vs230.6±26.2 ml/m^2, p&lt;0.001). Similarly, the capillary-small vessel blood flow (vessel cross sectional area &lt;5 mm^2) was reduced in the long COVID population (118±19 mL vs 132±23 mL, p=0.011). (Figure). The specific image-based airway volume of the distal lung regions was lower than that of the healthy population (11.1±6.74 mL vs 17.33±7.7 mL, p&lt;0.05). Conclusions: Both the reduced global and capillary pulmonary blood flow, and distal airway volumes indicate impaired gas exchange and might explain the pulmonary complaints of patient with long COVID syndromes even severe months after Coronavirus infection.
Abstract 14480: Safety and Efficacy of Direct Oral Anticoagulants vs Low Molecular Weight Heparin for Treatment of Venous Thromboembolism in Patients With Cancer
Authors: Sahib Singh, Udaya Tantry, Kevin Bliden, Paul Gurbel
Journal: Circulation (2023)

Introduction: Direct oral anticoagulants (DOACs) have been studied for treatment of venous thromboembolism (VTE) in patients with cancer. However, the trials have shown conflicting results when compared with low molecular weight heparin (LMWH). Therefore, we aimed to conduct an updated meta-analysis of the available studies. Methods: Randomized controlled trials (RCTs) comparing DOAC vs LMWH for VTE treatment in cancer patients were searched from multiple online databases. The primary endpoints of interest were recurrent VTE, major bleeding, clinically relevant non major bleeding (CRNB) and mortality at the longest available follow up. A random-effects model was used to estimate risk ratios (RR) with 95% confidence intervals (CI). Results: Six RCTs, with a total of 3,703 patients - 1,855 in the DOAC group and 1,848 in the LMWH group were included. Around 49% of patients were men and the mean age was 66 years. The follow up duration varied from 3 to 24 months. Patients treated with DOAC, when compared with the LMWH group, had lower risk of recurrent VTE (RR 0.66, 95% CI 0.52-0.83, p = 0.0005) (Figure 1), but a higher risk of CRNB (RR 1.63, 95% CI 1.19-2.23, p = 0.002). No significant differences were found between the two groups with regards to major bleeding (RR 1.19, 95% CI 0.82-1.71, p = 0.36) (Figure 2) or overall mortality (RR 1.02, 95% CI 0.90-1.14, p = 0.78). Conclusions: For treatment of VTE, DOACs as compared with LMWH are associated with significant reduction of recurrent VTE events but with a higher risk of CRNB.