tbuckley/cabot-search huggingface dataset:
Abstract 4142792: VA Lipid Optimization Reimagined Quality Improvement Project (VALOR-QI) at the Dallas VA
Authors: Anupriya Bhatnagar, Ananda Bryant, Daryoush Shahin, KYAW SOE
Journal: Circulation (2024)

The Dallas VA is one of the 50 VA sites participating in a national quality improvement initiative called VALOR-QI: VA Lipid Optimization Reimagined Quality Improvement Project. VALOR-QI is a collaborative project between the U.S. Department of Veterans Affairs (VA) and the American Heart Association (AHA) with the goal of positively impacting veterans’ cardiovascular (CV) health. As part of the program, VA sites work with an AHA QI Consultant to develop and deploy a local quality improvement plan to help overcome site specific barriers preventing veterans from achieving optimal cholesterol levels. We hypothesize that the QI strategies implemented will positively impact lipid levels and ultimately CV outcomes among high-risk patients. We aim to assess potential barriers to achieving LDL-C &lt;70 mg/dL and develop efficient ways to maintain LDL-C goal. Our approach to the VALOR-QI program at Dallas VA is by enrolling patients with established ASCVD and LDL-C &gt; 70 mg/dL from cardiology, vascular, diabetes, lipid, and independent PharmD clinics. These patients are followed by a health coach every 2- 6 months. Medical adherence is enforced by the health coach ensuring timely refills and reminders. Lifestyle modifications are encouraged via educational materials, referral to dieticians, recreation classes, and tobacco cessation. Patients are also encouraged to sign up for patient portal (my HealtheVet) to access electronic medical records and expedite communication with their healthcare team. The health coach provides individualized counseling regarding lipid lowering treatment and acts as liaison between patients and their providers. VALOR-QI was launched at Dallas VA in Jan 2023. As of May 17 th , 2024, an interim analysis showed that out of 132 veterans engaged, 49 (37.1%) achieved target LDL-C, 66 (50%) received educational material, 4 (3.03%) were referred to dieticians, 10 (7.58%) were referred to recreation programs, and 4 (17.4% of active smokers) were interested in quitting. In conclusion, our VALOR-QI strategy at Dallas VA showed encouraging results, but it is premature to make final conclusions. The support of a health coach showed improved medication adherence, health literacy, and lifestyle modification, thus achieving LDL-C target. Major barriers to achieving target LDL-C were health literacy about high cholesterol, challenges in navigating the health care system, and treatment inertia among patients and providers.
Abstract Sa1101: Association Between Changes in Hypoxic-Ischemic Brain Injury and Neurological Outcomes in Cardiac Arrest Survivors.
Authors: So Young Jeon, Jung Soo Park, Changshin Kang, Yeonho You, Jin Hong Min, Wonjoon Jeong, Hong Joon Ahn, YONGNAM IN
Journal: Circulation (2024)

Aim: Quantitative analysis of hypoxic-ischemic brain injury (HIBI) using apparent diffusion coefficient (ADC) values from brain magnetic resonance imaging (MRI) is used to predict poor neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors. Our study aimed to determine the association between changes in HIBI and neurological outcomes in OHCA survivors using two types of MRI. Methods: This observational study used data collected prospectively from a tertiary academic hospital. The study included adult comatose OHCA survivors who underwent targeted temperature management (TTM) and brain MRI within 6 hours (first) and 72–96 hours (second) using the same MR scanner. We analyzed the neurological outcomes based on brain volumes below a specific ADC value using 10-step intervals within the range of 200–1200 × 10 -6 mm 2 /s for the first and second MRIs. ADC-R(x) represents the proportion of total brain volume occupied by voxels, with ADC values ranging from 200 × 10 -6 mm 2 /s to each threshold. Additionally, ADC(x) represents the proportion of total brain volume occupied by voxels that are “threshold - 10” at each threshold. Poor neurological outcomes were categorized as cerebral performance levels 3–5, observed 6 months after OHCA. Results: Overall, 122 patients (25% female) were included in the analysis, of whom 61 (50%) showed poor neurological outcomes. Higher ADC-R(x) were observed in the poor neurological outcome group on both the first and second MRI scans at all ADC intervals (all P &lt; 0.05) (Figure 1). In the Good Neurological Outcome group, the ADC-R values ranged between 370 and 940, with the second MRI value being smaller than that of the first (right shift, P &lt; 0.05). In contrast, the Poor Neurological Outcome group showed ADC-R values ranging between 340 and 1190, with the second MRI value being higher than that of the first (left shift, P &lt; 0.05) (Figure 2). The difference in ADC(x) between the second and first MRI based on neurological outcome showed a positive change in ADC below 620 for a poor neurological outcome and a positive change in ADC above 740 for a good neurological outcome (Figure 3). Conclusions: In this cohort study, we observed that the initial HIBI that occurred during OHCA worsened or returned to normal depending on the neurological outcome after TTM. Prospective multicenter studies are required to generalize our findings.
Abstract 4145802: Association between Glucagon-like peptide-1 receptor agonists and risk of Arrhythmias or Heart Failure among patients with Type 2 Diabetes: A Meta-Analysis of 29 Randomized Controlled Trials.
Authors: Vikash Jaiswal, Akash Jaiswal, Kriti Kalra, FNU Danisha, Jishanth Mattumpuram, Monodeep Biswas
Journal: Circulation (2024)

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a reduction in major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM). However, their effect on reducing the risk of incidence of arrhythmias and heart failure has not been established, and there is very limited literature to date. Objective: We evaluated the effect of GLP-1 RAs on the incidence of arrhythmias and heart failure among patients with T2DM. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that enrolled patients with type 2 diabetes and compared GLP-1 RAs and control groups. PubMed and ClinicalTrials.gov were systematically searched from inspection till May 2024 without any language restrictions. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model. Results: A total of 29 RCTs with 72,868 patients (35,631 in the GLP-1 RA group and 37,237 in the control group) were included in the analysis. Pooled analysis showed that there is no significant association between GLP-1 RAs and incidence of atrial fibrillation (OR, 0.94(95%CI: 0.75-1.18), P=0.60), atrial flutter (OR, 0.87(95%CI: 0.60-1.26), P=0.46), cardiac arrest (OR, 0.79(95%CI: 0.51-1.23), P=0.30), ventricular tachycardia (OR, 1.37(95%CI: 0.90-2.07), P=0.14), and ventricular fibrillation (OR, 0.91 (95%CI: 0.45-1.84), P=0.80) when compared with control group. However, GLP-RAs reduced the incidence of atrioventricular block complete (OR, 0.58 (95%CI: 0.35-0.97), P=0.04), and heart failure (OR, 0.795 (95%CI: 0.634-0.997), P=0.047). Conclusion: This study shows that GLP-1 RAs reduced the incidence of atrioventricular block complete and incidence of heart failure. However, no significant association has been observed for arrhythmias.
Abstract 4135662: Dietary Inulin Improves Glucose Metabolism and Energy Balance in Obese Mice via Adipocyte Free Fatty Acid Receptor 2 (FFAR2)
Authors: Karolline May, Angel Lee, Shari Wang, Caeley Bryan, Martin Blaser, Brian Layden, Gregory Morton, Laura Den Hartigh
Journal: Circulation (2024)

Background: Inulin is a non-digestible prebiotic dietary fiber that can promote metabolic health including reduced body weight and improved glucose metabolism via effects on gut microbiota. We hypothesize that inulin prevents obesity-associated cardiometabolic alterations by augmenting the production of short-chain fatty acids (SCFA) from gut microbiota, which activate free fatty acid receptor 2 (FFAR2), a major SCFA receptor, in murine adipose tissue. Methods: 8-week-old male C57BL/6J (wild-type, WT; n=34) and adipocyte FFAR2-knockout (Ad-FFAR2 KO; n=25) mice were fed a high-fat high-sucrose (HFHS) diet for 8 weeks, then randomized into experimental groups to receive either continued HFHS (n=8-13), or HFHS containing inulin (10% w/w chicory root inulin; n=17-21) for a further 5 weeks. Body weight was recorded weekly, food intake, body composition, and indirect calorimetry were assessed before and after the inulin intervention, and intraperitoneal glucose and insulin tolerance tests were performed. Subcutaneous and visceral white adipose tissue (WAT) samples were collected at the study termination. Results: HFHS-fed Ad-FFAR2 KO mice showed higher body weight (7.4%), fat mass, and WAT weight due to increased food intake, with worse glucose tolerance compared to WT mice. In WT mice, inulin significantly reduced body weight gain and body adiposity. These effects were associated with reduced locomotor activity and respiratory quotient (RQ) without effects on energy expenditure and were accompanied by improvements in glucose tolerance. Strikingly, inulin had no effect on body weight or body adiposity in Ad-FFAR2 KO mice but reduced RQ, locomotor activity, and improved glucose tolerance similar to WT mice. Conclusions: Our findings suggest that FFAR2 signaling in adipose tissue is crucial for improving cardiometabolic outcomes in obesity and that gut metabolites responsive to dietary interventions, such as inulin, are potential targets for obesity treatment strategies.
Abstract 4136085: The Prognostic Impact of Thrombocytopenia at 6 months after Transcatheter Aortic Valve Replacement: A Retrospective Multicenter Study
Authors: Motoyoshi Takahara, Kan Zen, Takuma Iwaya, Tomotaka Fujimoto, Masaki Yashige, Michiyo Yamano, Tetsuhiro Yamano, Takeshi Nakamura, Satoaki Matoba
Journal: Circulation (2024)

Background: Transient thrombocytopenia after transcatheter aortic valve replacement (TAVR) is a common phenomenon. Thrombocytopenia after TAVR during the perioperative period has been reported to impact prognosis. However, the impact of thrombocytopenia in the mid-term post-TAVR period is currently unknown. Methods: A retrospective observational study was conducted on 1405 patients who underwent TAVR from May 2016 to February 2023 at four institutions. Of these, 850 patients were analyzed. Patients who underwent dialysis (67), converted to an open chest surgery (8), had a Valve-in-Valve procedure (30), underwent a direct aortic approach (16), had a malignant tumor (66), and patients whose platelet levels could not be measured at 6 months after TAVR due to death or dropout were excluded from the analysis. The clinical follow-up occurred at 1, 6, and 12 months after the procedure. Laboratory testing was conducted before TAVR, during the perioperative period, 1 month post-procedure, and 6 months later. The decrease in platelet count (DPC) 6 months after TAVR was calculated by the following formula: [(Baseline platelet – 6 months platelet)/baseline platelet *100]. A receiver operating characteristics curve was plotted for all-cause mortality at 1 year and DPC at 6 months. The calculated cutoff value for the DPC at 6 months (28.68%) was utilized to classify and compare the two groups. Multivariate logistic regression models were also used to examine the association between the DPC at 6 months and all-cause mortality at 1 year. Adjusted for propensity score matching, the DPC was compared at 6 months in self-expandable and balloon-expandable prosthetic valves. Result: Of the 850 eligible patients (age: 85.5 ± 4.9 years), 31 (3.4%) died between 6 months and 1 year after TAVR. The DPC at 6 months after TAVR was 11.9 ± 22.5%. Multivariate logistic regression analysis including the DPC at 6 months, age, gender, and STS score showed that the DPC at 6 months was independently associated with all-cause mortality at 1 year (odds ratio: 1.03, 95% confidence interval: 1.005-1.046, p=0.01). After adjustment for propensity score matching, the balloon-expandable prosthetic valve had a higher rate of thrombocytopenia at 6 months (15.0% vs. 9.6%, p=0.04). Conclusion: The DPC at 6 months after TAVR may predict all-cause mortality at 1 year.
Abstract 4139162: Optical coherence tomography measures mechanical contractile properties of the beating murine heart
Authors: Yirong Zhou, Junyoung Kim, Guillermo Tearney, Aaron Aguirre
Journal: Circulation (2024)

Introduction: Optical imaging techniques can characterize properties of tissue at high temporal and spatial resolution, offering unique insights into electrically excitable tissues such as nerve and muscle. We hypothesized that the gated high-speed optical coherence tomography (OCT) could profile the contractile properties of mouse myocardial tissue and facilitate investigations of microscale mechanical function in the beating heart. Methods: C57BL/6 male mice (n=6) underwent a sternotomy while anesthetized and ventilated and were imaged at baseline with OCT. Another cohort of C57BL/6 male mice (n=6) were sacrificed and the hearts were ex vivo perfused with crystalloid using a Langendorff system. These hearts were imaged at baseline and after inhibition of contractile function with blebbistatin. OCT was performed using a custom tissue stabilizer and a Thorlabs TEL 321 OCT system, which was synchronized to physiologic signals using custom hardware and software and cardiac pacing protocols (Fig. 1A and 1B). OCT cross-sectional B-scan images (Fig. 1C) were obtained throughout multiple cardiac cycles in both in vivo and ex vivo preparations. Data were processed in MATLAB and ImageJ using the workflow in Fig. 1D. Results: Highly reproducible cross-sectional mean intensity changes were observed over the contractile cycle in vivo and ex vivo (Fig. 1E, left and middle). With mechanical contraction inhibited by blebbistatin, this cyclical intensity extinguished, linking the optical scattering change measured by OCT to myocardial contraction (Fig. 1E, right). B-scan curves averaged over multiple mice and temporally aligned with the ECG waveform (Fig. 1F) demonstrate a signal intensity waveform that reproducibly varies with the contractile cycle for both in vivo and ex vivo preparations. In vivo and ex vivo baseline waveforms both had peak intensity during systole and minimum in end-diastole (Fig. 1F). Reproducibility in ex vivo beating heart preparations without blood perfusion provides evidence that myocardial mechanical properties, not red blood cell flow, generate the intensity changes. Conclusion: Gated high-speed OCT imaging can quantify the mechanical contraction wave in the myocardium. Combined with gated OCT angiography, OCT techniques will provide high resolution imaging of both blood flow and mechanical contractility of the beating heart in small animal models of heart disease.
Abstract 4148077: Heart Failure Mortality Between 1990 and 2020 by US State and Racial and Ethnic Group
Authors: Laura Fleszar, Henry Dorsey, Catherine Johnson, Gregory Roth
Journal: Circulation (2024)

Introduction: Heart failure (HF) mortality rates in the US appear to have increased in the past decade. It is unknown how these have changed in recent years by racial and ethnic groups within states. Research Question: To understand disparities in HF mortality patterns between 1990 and 2020 Aim: To estimate the change in HF mortality rates between 1990 and 2020 for Hispanic, non-Hispanic Black, and non-Hispanic White males and females in each US state Methods: We used multiple cause of death records from the National Vital Statistics System and population data from the National Center for Health Statistics to estimate HF mortality from 1990 to 2020 by state, age group, sex, and racial and ethnic group. A binomial model was fit to the data using RegMod, a Bayesian extension of a generalized linear model which incorporated priors from a hierarchy and modeled year as a spline. Results: In 2020, we estimated 566230 (95% UI 566160 to 569740) deaths due to HF. Between 1990 and 2010, HF rates declined in general for all racial and ethnic groups across the US, but not consistently for all states (Figure). From 2010 to 2020, this trend reversed, with age-standardized mortality from HF increasing over this time period, but again this change was not consistent across states. Among the Hispanic population, mortality increased for all states except for Maine, with the largest change for both sexes in Oklahoma. For the non-Hispanic, Black group, mortality increased among all states, with the largest change for both sexes in Oklahoma and South Dakota. Among the non-Hispanic, White populations, mortality decreased for both sexes in District of Columbia, while the largest increases were in Oklahoma. Conclusion: Heart failure mortality increased in the past decade, with striking increases in specific locations by race and ethnic group. Identifying etiologies and drivers of increased HF deaths, including the role of new therapies for subsets of systolic function, could help target novel therapies to subpopulations at highest risk. Differences in trends by state and race and ethnicity groups provides important information for clinicians and policymakers interested in reducing mortality rates.
Abstract 4144583: Beyond Acute Rejection Screening Following Pediatric Heart Transplant: In Patients Negative for Rejection, Elevated Donor-Derived Cell-Free DNA is Associated with Cardiac Allograft Vasculopathy (CAV) and Donor Specific Antibodies (DSA)
Authors: Benjamin Olsen, Jason Cole, Scott Auerbach, Kathleen Simpson, Melanie Everitt
Journal: Circulation (2024)

Donor-derived cell-free DNA (dd-cfDNA) has been increasingly used to detect acute rejection (AR). We aimed to compare our institutional dd-cfDNA results to previously published adult and pediatric dd-cfDNA AR cutoffs. We also hypothesized that in the absence of AR, elevated dd-cfDNA would be associated with CAV and positive DSA. Patients (pt) &lt; 18 years at transplant with &gt; 1 dd-cfDNA between 2021-2023 were included. Using dd-cfDNA levels from this cohort, sensitivity, specificity, NPV, and PPV were calculated. False positives and false negatives (FN) were determined using published dd-cfDNA thresholds. AR was defined as decision-to-treat with increased immunosuppression, which was independent of dd-cfDNA in our cohort. In pt without AR, t -test was used to compare the means of dd-cfDNA levels in pt with and without DSA. χ 2 testing was then performed to evaluate the association between dd-cfDNA levels above and below 0.2% and the presence/absence of DSA and CAV. DSA was defined as allele-specific DSA identified by single antigen bead with mean fluorescence intensity &gt;1000, and CAV as any disease by angiography. There were 379 samples among 163 pt, a median of 2 samples per pt, and 32 samples obtained at time of AR. Performance of dd-cfDNA in our cohort vs published dd-cfDNA thresholds is shown in Table 1. The FN rate ranged from 16 to 37% as the dd-cfDNA threshold increased. Mean dd-cfDNA was higher in patients with positive DSA versus those without (0.83% vs 0.19%, p&lt;0.001). In patients that did not meet AR criteria, dd-cfDNA levels &gt; 0.2% were associated with a higher prevalence of positive DSA (n=66) (48% vs 13%, p&lt;0.001), and trended towards a higher prevalence of CAV (n=20) (15% vs 11%, p=0.08). Dd-cfDNA had high sensitivity and NPV for AR but the FN rate using published dd-cfDNA cutoffs was high in our validation cohort. The clinical utility of dd-cfDNA may extend beyond AR screening given increased frequency of DSA and CAV in pt with elevated levels that are negative for AR. We speculate that monitoring intra-pt dd-cfDNA variability will reduce the FN rate when screening for AR in addition to enhancing its clinical utility when monitoring for CAV and DSA.
Abstract 4146303: A Single-Dose of a Novel CasX-Editor Lowers APOC3 Levels In Vivo
Authors: Santhosh Karanth, Simon Bucher, Elena Smekalova, Jennifer Saraya, Shannon Stein, Anna Sato, ShyamSundhar Bale, Oleh Krupa, Anthony Mauriello, Sterling Ripley-Phipps, Katherine Miller, Ali Su, Anna Mrak, Maitreyee Karmarkar, Michelle Eggers, Farah Bardai, Lokesh Narsineni, Yuexuan Li, Heera Langner, Keith Szulwach, Natalie Goh, Amanda Mok, Kirsten Reimer, Benjamin Oakes, Aarif Khakoo, Maria Mirotsou
Journal: Circulation (2024)

Background: Apolipoprotein C-III (APOC3) is a key regulator of lipid metabolism that inhibits the catabolism and clearance of triglyceride (TG)-rich lipoproteins in the blood. Loss-of-function APOC3 variants are associated with significantly lower TG levels and a reduced risk of heart disease, underscoring the potential of APOC3 inactivation as a therapeutic strategy for patients with familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (SHTG). Here, we developed STX-1400 lead molecules as a novel investigational gene editing treatment using a highly engineered CRISPR-CasX mRNA and a guide RNA (gRNA) encapsulated into lipid nanoparticles (LNPs) to edit the APOC3 gene and knock out its hepatic expression. Methods: STX-1400 lead molecules were evaluated for editing potency and resulting functional effects on APOC3 reduction in vitro in primary human hepatocytes (PHHs) and primary cynomolgus hepatocytes (PCHs). In vivo studies were conducted in PXB mice, a humanized liver mouse model. Liver biopsies and serum samples were collected at two weeks post-dose. Human APOC3 mRNA and APOC3 protein levels were measured in liver biopsies and serum samples, respectively. Lipid profile evaluation, which included measuring TGs and total cholesterol (TC) levels, was also performed. Results: Treatment of PHHs with LNPs containing STX-1400 lead molecules showed a dose-dependent increase in editing activity; up to 90% editing at the APOC3 locus was associated with &gt;70% reduction in secreted APOC3 protein levels. Potency was also observed in PCHs, with up to 70% editing. A single dose of LNPs encapsulating STX-1400 lead molecules delivered into PXB humanized mice resulted in &gt;60% editing at the APOC3 locus in the liver, which was associated with &gt;90% reduction of serum hAPOC3 protein levels, accompanied by reduction in TG and TC levels. Conclusions: These data demonstrate that the STX-1400 lead molecules efficiently knock down hepatic expression of APOC3 in preclinical models. This work suggests that the CRISPR-CasX-based editor approach could be developed as a single dose therapy for the treatment of hypertriglyceridemia.