tbuckley/cabot-search huggingface dataset:
Abstract 17387: The Ketone Body Beta-Hydroxybutyrate Attenuates Cardiomyocyte Hypertrophy Independent of BDH1-Mediated Oxidation
Authors: Timothy R Matsuura, Mitja L Karwowski, Fawaz Naeem, Ling Lai, David Scott, B D Westenbrink, Daniel P Kelly
Journal: Circulation (2023)

Previously, we and others identified evidence for increased myocardial ketone body oxidation in failing mouse and human hearts and demonstrated that increased levels of beta-hydroxybutyrate (ßOHB), the most abundant ketone body, reduced pathologic cardiac remodeling in preclinical models of heart failure. To better understand how ßOHB prevents pathologic cardiac hypertrophy, we sought to determine whether: 1) ßOHB has direct effects on cardiomyocyte (CM) hypertrophy; and 2) if ßOHB oxidation is required for this effect. CMs were isolated from hearts of adult male C57BL/6 cardiac-specific beta-hydroxybutyrate dehydrogenase 1 knockout (csBDH1KO) mice and wildtype (WT) littermate controls. csBDH1KO CMs are unable to oxidize ßOHB given that BDH1 catalyzes the first step of R-ßOHB oxidation. CMs were cultured in media containing 5.5mM glucose ± 3mM R-ßOHB in the presence or absence of the hypertrophic agonist phenylephrine (PE, 100μM). CM width and length were quantified to assess hypertrophic growth. Stimulation with PE increased CM width:length ratio compared to glucose control by 31% and 33% in WT and BDH1KO CMs, respectively. Addition of R-ßOHB in the absence of PE had no effect on CM morphology, whereas R-ßOHB limited PE-induced increases in width:length ratio to 2% and 4% in WT and BDH1KO CMs, respectively (p&lt;0.01 vs PE without R-ßOHB). In addition, PE-induced hypertrophy was prevented in WT CMs treated with S-ßOHB (this stereoisomer cannot be oxidized). To confirm that the cultured CMs utilized ßOHB, WT and BDH1KO CMs were cultured in media containing [U- 13 C] R-ßOHB. Stable isotope tracing showed significant fractional enrichment of citrate by R-ßOHB in WT CMs with limited enrichment in BDH1KO CMs (17.8% vs 4.5%, p=0.02). These findings support a role for ßOHB-mediated attenuation of cardiac hypertrophy through direct action on CMs via a mechanism independent of BDH1-mediated oxidation. Taken together with our previous results, these findings strongly suggest that ketone bodies improve heart failure by providing both oxidation-dependent (fuel source) and oxidation-independent as yet undefined cardioprotective mechanisms.
Abstract 17200: PAD Raising Awareness in Sacred Environments “Praise”
Authors: Victoria Thomas, Marjorie Butler, LaPrincess C Brewer, DanDan Liu, Ine Sohn, Emily Shardelow, Aaron W Aday, Joshua A Beckman
Journal: Circulation (2023)

Introduction: Atherosclerotic peripheral artery disease (PAD) leads to a great burden of cardiovascular and limb-related morbidity and mortality in African Americans (AA) compared to White Americans. Medical center partnerships with churches may be an effective method to improve PAD awareness and detection in the AA community. Hypotheses: We hypothesized that implementing a medical educational program in partnership with churches would increase PAD familiarity and identify participants with undiagnosed PAD. Aims: To determine (1) PAD familiarity before and after a one-time educational intervention and (2) the prevalence of PAD in older, church-going Nashville residents. Methods: Using a community-engaged research (CER) model, we partnered with 5 churches to enroll participants ≥ 50 years of age. Participants were given a 16-point pre- and post-educational program assessment to determine baseline and post-intervention PAD knowledge. Pre- and post-intervention scores were compared using Wilcoxon signed-rank test. Ankle-brachial index (ABI) testing was used to screen for PAD (ABI &lt; 0.9). Results: We enrolled 120 participants (mean age [SD]: 64.67 [8.33] years, 74% women, 80% AA). The prevalence of PAD was 10.83%. Pre-intervention PAD awareness was low (mean score (MS): 10.89 [4.24]) and improved significantly post-intervention in all participants (MS: 13.88 [2.76; p=2 x 10 -12 ). Participants without PAD (ABI ≥ 0.9-1.39) (MS: 10.81 [4.28] vs. 13.91 [2.79]; p= p=4 x 10 -11 ) and with indeterminate status (ABI&gt;1.4) (MS [SD]: 10.00 [5.03] vs. 14.10 [1.73; p=0.01) showed significant improvement in PAD awareness pre vs post intervention. Participants with PAD (ABI &lt;0.9) (MS: 12.15 [3.26] vs. 13.46 [3.26; p=0.40) did not have significant improvement in their awareness scores. Conclusions: The PRAISE study demonstrates an effective CER partnership with churches as a method to increase PAD awareness and early detection of PAD, specifically among AAs.
Abstract 12831: Serum Potassium Levels and Mortality in Heart Failure Patients. A Meta-Analysis
Authors: Jia Ee Chia, Song Peng Ang, Vikash Jaiswal
Journal: Circulation (2023)

Introduction: Serum potassium disturbances are frequently observed in patients with heart failure (HF) and can be attributed, to some extent, to comorbidities and the use of diuretics, mineralocorticoid receptor antagonists, and renin-angiotensin-aldosterone system antagonists. Previous studies on the prognostic implications of potassium homeostasis impairment have yielded heterogeneous findings. This meta-analysis aims to evaluate the association between serum potassium levels and mortality in HF patients. Methods: A comprehensive search was conducted across various electronic databases, including PubMed, Embase, and the Cochrane Library, to identify relevant studies. The primary outcomes assessed were all-cause mortality and cardiovascular mortality. The DerSimonian-Laird random-effects model was used to pool the outcomes, and the results were presented as hazard ratios (OR) with 95% confidence intervals (CI). Meta-regression was performed to identify potential sources of heterogeneity. Results: A total of twelve studies involving 45,678 HF patients were included in the analysis. Among them, 3,298 patients were hypokalemic, 38,328 were normokalemic, and 4,052 were hyperkalemic. The follow-up period was 1.5 (1- 2.8) years. The meta-analysis of adjusted effect sizes revealed that both hypokalemia (HR 1.68, 95% CI: 1.38-2.05, p &lt; 0.001) and hyperkalemia (HR 1.36, 95% CI: 1.17-1.57, p &lt; 0.001) were significantly associated with increased all-cause mortality. When compared to normokalemic patients, those with hypokalemia had a significantly higher risk of cardiovascular mortality (HR 1.77, 95% CI: 1.02-3.07, p = 0.01), whereas no significant association was found for hyperkalemia (HR 1.13, 95% CI: 0.98-1.31, p = 0.10). Univariate meta-regression analysis did not identify any significant moderators of effect size. Conclusions: This study reveals a U-shaped relationship between serum potassium levels and all-cause mortality in patients with heart failure. Hypokalemia is additionally associated with cardiovascular mortality.
Abstract 17307: Pre-Existing Endoplasmic Reticulum (ER) Stress Inhibits Sars-Co-V2 Entry Into Host Cells Through Modulation of AKT Signaling and Unfolded Protein Response (UPR)
Authors: Ahmed A Bakillah, Sindiyan Al Shaikh Mubarak, Abeer Al Otaibi, Fatimah Al Hejji, Abdulrahman Almasaud, Haya Al Jami, Badr AlSubai, Jahangir Iqbal, Naif Khalaf Alharbi, Ali Ahmed Al Qarni
Journal: Circulation (2023)

Introduction: It is well known that SARS-Co-V2 infection can induce ER stress-associated activation of unfolded protein response (UPR) in various host cells which may contribute to the pathogenesis of COVID-19. However, the interplay between SARS-Co-V2 infection and UPR signaling in pre-existing ER stress associated pathological conditions has not been well elucidated. Hypothesis: We hypothesized that modulation of a pre-existing ER stress in host cells could attenuate susceptibility to SARS-CoV-2 infection by activating a range of cellular defense. Methods: Increasing concentrations of Tunicamycin (Tm) and Thapsigargin (Tg) have been used to induce ER stress in Huh-7 cells. After 6h treatment, cells were infected with SARS-CoV-2 pseudotyped particles (SARS-CoV-2pp) for 48 p.i. SARS-Co-V2-2pp entry was measured using Bright Glo TM luciferase assay. Cell viability was measured by cell titer Glo ® luminescent cell viability assay. The mRNA and protein expression of UPR markers were evaluated using RT-qPCR and Western blot methods. Results: Tm (5 μg/ml) and Tg (1 μM) efficiently inhibited SARS-CoV-2pp entry into cells without any cytotoxic effect. Chemical ER stress-induced inhibition of SARS-CoV-2pp entry was associated with significant reduction of ACE2 expression in Tg-infected cells but not with Tm. Strikingly, Tm and Tg revealed differential effects in modulating the expression of ER stress genes in infected cells. Both Tm and Tg significantly reduced the expression of stress-inducible ER chaperone GRP78/BIP in infected cells. In contrast, the IRE1-XBP1s and PERK-eIF2α-ATF4-CHOP signaling pathways were downregulated in Tg-infected cells only. Additionally, insulin-mediated glucose uptake, phosphorylation of Ser 307 IRS-1 and downstream p-AKT were enhanced in Tg-infected cells without any change in ERK phosphorylation. Conclusions: These findings suggest that pre-existing ER stress could modulate a specific UPR response in infected cells capable of counteracting the stress-inducible elements signaling, thereby depriving SARS-Co-V2 of essential components for their entry and replication. Pharmacological manipulation of ER stress in host cells might provide new therapeutic strategies to alleviate SARS-CoV-2 infection.
Abstract 18568: Machine Learning Model for the Prediction of Early Discharge of Patient Underwent Transcatheter Aortic Valve Replacement Using Electronic Medical Record
Authors: Xiang Li, Hui Ren, Yee-Ping Sun, Benjamin Scirica, Quanzheng Li
Journal: Circulation (2023)

Introduction: With the increasing experience in TAVR, early discharge (within 24 to 72 h) has become a goal to accelerate patient recovery. Several studies suggest the possibility of safe, early discharges. But there is little consensus and considerable variation in early discharge protocols. Optimizing patient selection for early discharge can avoid prolonged hospital stays and save substantial costs without sacrificing patient safety. Hypothesis: The decision for early discharge after TAVR can be modeled and predicted by a machine learning model based on EMR data. Methods: Detailed demography, laboratory, medications, and comorbidities data from the EMR of all 1075 TAVR patients at Brigham and Women's Hospital from 2017-22 were included in a Random Forest machine learning model to make a binary prediction of whether the patient will be discharged within 36 hours after the procedure. We performed a 10-fold cross-validation experiment using the proposed model on the 1075-patient data. Receiver-operating characteristics (ROC) evaluated the prediction accuracy and uncertainty of the model, and clinical outcomes of patients with early discharge were evaluated by 6-month readmissions. Results: The mean age was 81± 9 years; 57% were male. The median length of stay was 51.3 hours. A total of 481 (44.7%) were discharged within 36 hours. Only 12 patients in this cohort were admitted with 24 hours. The average area under the ROC curve (AUC) of the 10-fold cross-validation was 0.83 (SD 0.04). (Figure) A total of 76 (7.1%) patients were readmitted due to cardiovascular reasons within 6 months, including 16/481 (3.3%) early-discharge patients vs. 60/594 (10.1%) non-early discharge patients (p&lt;0.001). Conclusions: Our model accurately predicts early (36 hours) discharge after TAVR, indicating the feasibility of utilizing machine learning to develop an EMR-based patient risk stratification and early discharge protocol.
Abstract 16875: Prothrombin Complex Concentrate is Superior to Fresh Frozen Plasma for the Management of Bleeding in Patients Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis
Authors: Patricia Viana, Jessica Hoffmann Relvas, Marina Zanchi Persson, Thamiris Dias Delfino Cabral, Jessica Sales de Oliveira, Jorge Eduardo Zanchi Persson, Paulo A Bonow, Camila Veronica Souza Freire, Camilo Velasquez, Sara Amaral
Journal: Circulation (2023)

Introduction: Prothrombin Complex Concentrate (PCC) and Fresh Frozen Plasma (FFP) are commonly used for management of bleeding in cardiac surgery patients. However, the relative efficacy and safety of these two strategies remain uncertain. Hypothesis: We conducted a meta-analysis to compare outcomes of PCC vs. FFP in patients who undergo cardiac surgery complicated by bleeding. Methods: PubMed, Embase, and Cochrane were searched for studies comparing PCC vs. FFP in patients who have cardiac surgery complicated by bleeding. Review Manager 5.4 was used for statistical analysis. Binary and continuous outcomes were compared with pooled odds-ratio and mean differences, respectively. The meta-analysis protocol was registered prospectively in PROSPERO. Results: We included 8 studies with 1,500 patients, of whom 613 (40.9%) received PCC. The mean follow-up period ranged from 28-90 days. The PCC group had significantly lower chest tube drainage at 24 hours (MD -148.50 mL; 95% CI -253.02 to -43.99 mL; p = 0.005; I 2 = 42%; Figure 1A). Also, there were fewer units of RBC transfusion within the first 24 hours (MD -1.02 units; 95% CI -1.81 to -0.24 units; p = 0.01; I 2 = 56%; Figure 1B) and fewer patients requiring RBC transfusion within the first 24 hours (OR 0.38; 95% CI 0.28-0.52; p &lt; 0.001; I 2 = 3%) in the PCC group. There was no significant difference between groups in all-cause mortality, thromboembolic events, stroke, or length of hospital stay. A subgroup analysis restricted to RCTs showed a significant reduction in the number of patients requiring RBC transfusion within 24 hours with PCC relative to FFP (OR 0.51; 95% CI 0.27-0.95; p = 0.04; I 2 = 0%). Conclusion: These findings suggest that PCC is an effective strategy compared with FFP in reducing chest tube drainage and the need for RBC transfusion within the first 24 hours in patients who undergo cardiac surgery complicated by bleeding, without a significant difference in mortality or thromboembolic events between groups.
Abstract 16989: Clonal Hematopoiesis of Indeterminate Potential Status is Associated With Left Main Artery Stenosis
Authors: Brett Heimlich, Michael Raddatz, John Wells, Caitlyn Vlasschaert, Sydney Olson, Marcus Threadcraft, Kristoff Foster, Emmanuel Boateng, Yan Ru Su, Colin Barker, Alexander G Bick
Journal: Circulation (2023)

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) occurs secondary to acquired mutations in bone marrow progenitor cells. CHIP confers a twofold risk of atherosclerotic cardiovascular disease (ASCVD). The two most common CHIP mutations are ten eleven translocase 2 (TET2) and DNA methyltransferase 3A (DNMT3A). However, there is limited data on specific cardiovascular phenotypes in this population. Methods: We recruited patients from the Vanderbilt University Medical Center cardiac catheterization laboratory and performed next generation sequencing to assign CHIP status. Multivariable logistic regression models and proportional odds models were used to assess the association between CHIP status and coronary angiography. Results: We sequenced 1,469 patients, and 1,149 had complete angiographic data. Of these, 214 (18.6%) had CHIP mutations with a variant allele frequency of &gt;2%. CHIP patients were significantly older (68 vs. 59 years, p = 7.7 x 10-16). CHIP carrier status was significantly correlated with any stenosis and degree of stenosis in the left main (LM) coronary artery (OR 1.87 [1.28-2.74]; P = 0.0013 and OR 2.12 [1.42-3.15]; P = 2.2 x 10-4). This association was stronger among patients with TET2 CHIP, both for any LM stenosis (OR 2.98 [1.48 - 5.96]; P = 0.0021) and the degree of LM stenosis (OR 3.52 [1.78 - 6.95]; P = 2.9 x 10-4) (Fig. 1). TET2 CHIP was also correlated with obstructive (&gt;70%) stenosis in any vessel (OR 2.28 [1.15 - 4.52]; P = 0.019), and the number of obstructive stenoses across coronary vessels (OR 1.83 [1.04 - 3.23]; P = 0.037). Conclusions: This is the first description of a specific atherosclerotic phenotype in CHIP and serves as a basis for understanding enhanced morbidity and mortality in CHIP. Our findings reveal a population enriched for CHIP carriers in the catheterization laboratory, an important observation for future studies focused on secondary prevention in CHIP-related ASCVD.
Abstract 17028: Characteristics and Short-Term Outcome of Patients in the Program “Get With the Guidelines” - One Vietnamese Center Registry
Authors: NGA Q VU
Journal: Circulation (2023)

Background: “Get with the guidelines HF” is a program with the aim of properly applying heart failure treatment recommendations into clinical practice and improving the outcome of patients. This study evaluated the initial result of the implementation of the program in one Vietnamese center. Method: This is a prospective, one-center, observational registry in Hanoi Heart Hospital, Vietnam. Hospitalized heart failure patients over 18 years old with reduced and mild reduced left ventricular ejection fraction (LVEF) were enrolled. Data included demographic characteristics, comorbidities, discharge medications, and post-discharge appointment plans. Results: From September 2021 to December 2022, 749 patients were included in the study with a mean age of 65. The male and female ratio was 56.1% and 43.9% respectively. 65.3% of the patients had reduced LVEF and 34.7% had mild reduced LVEF. Coronary heart disease was the most popular comorbidity and was diagnosed in 44.6% of patients. At discharge, after excluding drug contraindications, the rate of prescribing of RASi drugs (ACEi, ARB or ARNI), beta-blocker, mineralocorticoid receptor antagonists (MRA), SGLT2i were 97.56%, 92.86%, 96.15%, 57.14%, respectively in Q4.2021. At discharge, the rate of using these 4 drugs in Q4.2022 was 99.15%, 100%, 100%, and 85.19%, respectively. The rate of patients receiving all 4 GDMT drugs according to ACC/AHA guidelines in Q4.2021 and Q4 2022 was 28.8% và 41.4%. The percentage of patients using 3 and 2 GDMT drugs in the times mentioned above was 33.3% and 35.4% and 24.2% and 14.8%, respectively. Short-term follow-up showed that 30-day re-admission was 2.94% and the 30-day mortality after discharge was 0%. Conclusion: “Get with the guidelines” helps to implement guidelines to daily practice, especially the use of GDMT drugs, and gives promising results to improve the outcome for patients with heart failure. Keywords: heart failure, GDMT, Get with the guideline
Abstract 18770: Understanding Patients’ Characteristics and Coronary Microvasculature: Early Insights From First US Coronary Microvascular Dysfunction Registry
Authors: Ilan Merdler, Brian Case, Giorgio A Medranda, Itsik Ben-Dor, Ron Waksman, Hayder Hashim
Journal: Circulation (2023)

Introduction: Coronary angiography falls short in accurately evaluating the coronary microcirculation. Fortunately, a new comprehensive invasive hemodynamic assessment method, which uses coronary flow reserve (CFR) and the index of microvascular resistance (IMR), provides enhanced diagnostic capabilities. Objective: We present our early real-world experience with invasive hemodynamic assessment of the coronary microvasculature in symptomatic patients with non-obstructive coronary artery disease (CAD) from the first US Coronary Microvascular Disease Registry (CMDR). Methods: The CMDR is a prospective, multi-center, standardized registry of patients with angina and non-obstructive CAD who underwent invasive hemodynamic assessment of the coronary microvasculature using the Coroventis CoroFlow Cardiovascular System (Abbott Laboratories, Chicago, Illinois). Comprehensive assessments, including resting full-cycle ratio (RFR), fractional flow reserve (FFR), CFR, and IMR, were performed on all patients. Results: The first 156 patients enrolled in the CMDR were analyzed; their mean age was 62.4 years and 65.6% were female. A substantial proportion (31.8%) of patients presented with a Canadian Cardiovascular Society Angina Score of 3 or 4. CMD was diagnosed in 39 of 154 patients (25.3%), with mean RFR of 0.89±0.43, mean FFR of 0.93±0.08, mean CFR of 1.8±0.9, and mean IMR of 36.26±19.23. None of the patients experienced in-hospital adverse events. Conclusions: Early results from CMDR patients show that invasive hemodynamic assessment of the coronary microvasculature is safe and effective for suspected CMD. Tailored medical therapy for microvascular angina was provided to diagnosed CMD patients. With ongoing patient enrollment, the CMDR aims to contribute valuable insights to the growing evidence base for CMD.
Abstract 17180: Association of Arterial Return Cannula Size With Survival in Adults Undergoing Venoarterial Extracorporeal Membrane Oxygenation: An ELSO Registry Analysis
Authors: Laura Aguilar Franco, Alvaro A Delgado, Daniela Hincapie Tabares, Roy Sriwattanakomen, lisa fleming, Pablo A Quintero, Jen Ho, Marwa Sabe, kevin kennedy, Arthur Reshad Garan, E. Wilson Grandin
Journal: Circulation (2023)

Introduction: Peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used to support critically ill adults with cardiogenic shock (CS), but the impact of arterial cannula size on survival remains poorly understood. Hypothesis: A smaller arterial return cannula will be associated with similar survival. Methods: We queried the ELSO registry for adults undergoing VA-ECMO from 2017-2022 and stratified them into small (&lt;16 Fr) versus large (≥16Fr) arterial cannula size. We restricted the cohort to patients with body surface area (BSA) 1.8-2.2 m 2 and excluded patients with a concomitant left ventricular venting device, central cannulation, and multiple ECMO runs. The primary outcome was 30-day in-hospital mortality and secondary outcomes included 24-hour lactate clearance and rates of on-support acute renal and liver injury. Results: Among 2963 adults receiving peripheral VA-ECMO without a concomitant left ventricular venting device, 491 (16.6%) patients had a small arterial cannula and 2,472 (83.4%) had a larger cannula. Patients with a larger cannula were more often male, had marginally higher BSA, a higher incidence of pre-ECMO organ failures, and more often had a distal perfusion cannula (Figure, panel A). There was no difference in 30-day mortality between patients with small (40.3%) versus large (42.9%) arterial cannula, p= 0.295 (Figure, panel B), which persisted after multivariable modeling: adjusted hazard ratio 0.97 (95% CI: 0.79-1.19, p= 0.78). Lactate clearance at 24 hours of ECMO support (Figure, panel C) and the rates of acute renal injury (37% vs 41%, p = 0.024) and hyperbilirubinemia (4.3% vs 4.3%, p = 0.96) were similar between the two arterial cannula size cohorts. Conclusion: For adult patients undergoing peripheral VA-ECMO support, the use of a smaller (&lt;16F) versus larger (≥16F) arterial return cannula was associated with similar rates of in-hospital mortality and metrics of end-organ perfusion.