tbuckley/cabot-search huggingface dataset:
Abstract 4141703: Body Mass Index and Waist-Hip Ratio -- Risk Factors for Aortic Valve Disease: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Chunxiao Zhang, Ethan Moser, ANNE EATON, Jeremy Van't Hof, Weihong Tang, Amil Shah, Aaron Folsom, Lin Chen
Journal: Circulation (2024)

Introduction: Aortic valve disease (AVD) is common among older adults. Although body mass index (BMI) has been reported to be a risk factor for aortic valve stenosis (AS), it is unknown whether BMI or waist-hip ratio (WHR) is associated with aortic valve insufficiency (AI). Additionally, it is unknown whether there is a stronger association between BMI/WHR with AVD among Blacks compared with Whites. Hypothesis: Higher BMI/WHR is associated with an increased incidence of AS and AI in the ARIC study, a community-based cohort of Black and White adults. Methods: The analysis involved ARIC participants with echocardiograms at visit 5 (2011-2013) and visit 7 (2018-2019). BMI and WHR were ascertained from visit 5 and standardized by standard deviation (SD). Incident AVD between visits 5 and 7 was classified as aortic valve sclerosis, isolated AI, and AS regardless of AI, according to AHA guidelines. A multinomial regression model adjusted for multiple potential confounding variables, including age, sex, race, education, smoking status, drinking, diabetes, systolic blood pressure, antihypertensive medications, coronary heart disease, HDL-C LDL-C, and eGFR. Results: Of 1931 participants included in the analysis (mean age of 73.5 ± 4.1 years, 59.7% female, and 23.2% Black), 572 participants (29.6%) had incident AVD (n = 345 sclerosis, 159 pure AI, 68 AS). Higher BMI at visit 5 was associated with a greater incidence of aortic valve sclerosis (OR: 1.34 per 1-SD (5.78 kg/m 2 ), 95% CI: 1.15-1.56) and AS (OR: 1.32, 95% CI: 1.00-1.74) but was not associated with AI. Higher WHR was associated positively with aortic valve sclerosis (OR: 1.17 per 1-SD (0.08 unit), 95% CI: 1.00-1.36), AS (OR: 1.44, 95% CI: 1.12-1.86), and also AI (OR: 1.24, 95% CI: 1.01-1.53) ( Table 1 ). There were no race-by-obesity interactions in all analyses. Conclusion: A higher BMI is associated with a higher risk of AS, but not AI. By contrast, increased WHR is a risk factor for both AS and AI. Further research is warranted to replicate this novel finding and define potential underlying mechanisms.
Abstract 4141344: Leadless Pacemaker vs. Transvenous Pacemaker in End Stage Kidney Disease: Insights from the Nationwide Readmission Database
Authors: Jurgen Shtembari, Sajog Kansakar, Azka Naeem, Norbert Moskovits, Dhan Shrestha, Monodeep Biswas, Binaya Basyal, Ghanshyam Shantha, James Storey, Daniel Katz
Journal: Circulation (2024)

Background: Leadless pacemakers offer a safe and effective alternative pacing strategy, crucial for patients with end-stage renal disease (ESRD) overcoming vascular access isues. However, there is limited data available on their use in this population. Methods: We utilized the Nationwide Readmission Database to extract data on all adult patients with ESRD who received either traditional transvenous or leadless pacemaker implantation from 2016 to 2021. We then compared in-hospital mortality, in-hospital complications, healthcare resource utilization, and 30-day readmission rates between these two groups. Results: A total of 6,384 patients (81.2%) were included in the transvenous pacemaker cohort, while 1,481 patients (18.8%) were in the leadless pacemaker cohort. In ESRD patients, leadless pacemaker implantation was associated with higher in-hospital complications compared to transvenous pacemakers, including cardiac complications (aOR 4.12, CI 1.70-9.98, p&lt;0.01), vascular complications (aOR 3.6, CI 1.40-9.26, p=0.01), and the need for blood transfusions (aOR 1.85, CI 1.32-2.60, p&lt;0.01). There was no difference between the cohorts in terms of in-hospital mortality and 30-day readmission rates. However, the median length of stay was longer for leadless pacemaker implantation (5 days vs. 4 days, p&lt;0.01), and the total hospitalization charges were higher ($139,826 vs. $93,919, p&lt;0.01). Conclusion: In conclusion, while LPM implantation in ESRD patients was associated with higher in-hospital complications and healthcare resource utilization compared to TVPM, there was no significant difference in in-hospital mortality and 30-day readmission rates. Further research is needed to understand the nature of these complications and optimize outcomes for ESRD patients undergoing LPM implantation.
Abstract 4141409: Partnering With an American Indian Community to Co-Design a Structural Heart Disease Program to Improve Cardiac Care
Authors: McCall Miller, Lisa Vaughn, LeCario Benashley, Billie Bones, Samantha Buonfiglio, Gwendena Lee-Gatewood, JT Nashio, Amanda Paxson, Alan Riley, Davalyn Rope, Rachel Sarnacki, Rhiannon Walker, Dawnafe Whitesinger, Andrea Beaton, Sarah de Loizaga
Journal: Circulation (2024)

Introduction: American Indians are disproportionately impacted by cardiovascular disease. Furthermore, echocardiographic screening within one American Indian Tribe demonstrated ~6% of Tribal members had undiagnosed structural heart disease (SHD). Strategies for scale up of SHD screening are needed to improve earlier diagnosis and outcomes. Aim: Partner with the community to co-develop a scalable model to enhance SHD diagnosis, care, and outcomes that is culturally and contextually relevant for the partnering Tribe. Methods: We utilized a five-phase community-based participatory research approach outlined in Figure 1. Results: A five-member community research leadership board was established to bridge the gap between our research team and the community, in order to increase acceptability and program sustainability. Four group level assessment (GLA) sessions included 163 community members and identified the following five priorities as essential to a SHD program: 1) heart health/ SHD education and awareness; 2) cultural considerations; 3) inclusive, multigenerational community engagement; 4) improved resources for general health and wellness; and 5) accessible, patient-centered healthcare with local cardiac care. Follow-up semi-structured interviews were conducted with 19 community members. Thematic analysis identified key program needs including: 1) system considerations; 2) program considerations; 3) resources; 4) community awareness; 5) individual considerations/factors. Five personas were created based on emergent themes from the interviews: The Skeptic, The Hard-to-Reach, The Health Enthusiast, The Community Connector, and The Cultural/Tribal Champion. These personas were validated in community design workshops and used to identify barriers and facilitators of a SHD program, generate solutions to identified barriers, and prioritize program components based on impact and feasibility. Conclusions: We partnered with one Tribe to identify and co-develop the relevant and impactful components for an SHD program. Next steps include testing of programmatic implementation to understand reach, effectiveness, adoption, implementation, and maintenance.
Abstract 4141024: Safety and Efficacy with DOACs versus Warfarin in Patients with Atrial Fibrillation and Liver Cirrhosis: A Systematic Review and Meta-Analysis
Authors: Zeeshan Sattar, Shahryar Khan, Farhan Sattar, Laila Zia, Mashal Alam Khan, M Danial Ali Shah, Amit Noheria
Journal: Circulation (2024)

Background: Atrial fibrillation (AF) is increasingly prevalent in patients with liver cirrhosis, which is associated with both bleeding and thromboembolism. Patients with cirrhosis have been excluded from randomized controlled trials on the efficacy and safety of anticoagulants in AF. We performed a systematic review to compare direct oral anticoagulants (DOACs) with warfarin in patients with AF and concomitant cirrhosis. Methods: We systematically searched Pubmed and Embase from inception to the present. The primary outcome of interest was the hazard ratio of major bleeding. Secondary outcomes included gastrointestinal bleeding, all-cause bleeding, and ischemic stroke/systemic embolism[AN1] . Random effects models were used to calculate the weighted pooled hazard ratios for the outcomes. A two-tailed p&lt;0.05 was considered statistically significant. Heterogeneity was assessed using the I2 index. Data analysis was performed using Revman version 5.4.1 (Cochrane). Results: We included 5 non-randomized observational studies on patients with AF and cirrhosis (N=13,838). Among these, 7,641 were on DOACs and 6,326 were on warfarin. Men comprised 69.8% of the DOACs group and 69.1% of the warfarin group. The average age was 70.4±8.27 years in the DOACs group and 69.72±7.76 years in the warfarin group. Patients using antiplatelets comprised 26.7% of the DOAC group and 24.1% of the warfarin group. The mean HAS-BLED score was 3.00 in the DOACs group and 2.99 in the warfarin group. Compared to warfarin, DOACs used for AF in patients with cirrhosis were associated with a lower risk of major bleeding (HR 0.67, 95% CI [0.59, 0.76], I2=0%, p&lt;0.00001), gastrointestinal bleeding (HR 0.64 [0.45, 0.91], I2=54%, p=0.01), and all-cause bleeding (HR 0.81 [0.72, 0.92], I2=16%, p=0.001). No difference was found in the incidence of ischemic stroke/systemic embolism (HR 1.09 [0.55, 2.15], I2=85%, p=0.81). Conclusion: Our systematic review of non-randomized studies demonstrates that DOACs, as compared to warfarin, reduce the risk of bleeding in patients with AF and concomitant liver cirrhosis, without any difference in risk of stroke.
Abstract 4141173: CMR can discriminate need for biopsy and rejection therapy in children post heart transplant
Authors: Ravi Vegulla, Nicolle Ceneri, Devika Richmann, Nicholas Mouzakis, Karin Hamman, joshua kanter, John Berger, Tacy Downing, Yue-Hin Loke, Steven Staffa, David Zurakowski, Russell Cross, Laura Olivieri
Journal: Circulation (2024)

Background: Heart transplantation remains definitive therapy for children with heart failure, but the burden of acute graft rejection remains. While adult data has shown cardiac magnetic resonance (CMR) offers reliable, non-invasive identification of graft rejection1-3, endo-myocardial biopsy (EMB) continues to be the gold-standard in children. Hypothesis: CMR can establish the presence/absence of rejection, guiding need for EMB and rejection therapy. Aims: To assess the (1) strength of CMR parametric mapping in discriminating presence of rejection (defined as need for new therapy), and (2) the ability of CMR to identify patients without rejection, negating the need for EMB. Methods: Pediatric heart transplant patients referred for EMB underwent concurrent noncontrast CMR with volumetry, flows, MOLLI T1 and T2 parametric mapping at 1.5T. Average and peak segmental native T1 and T2 were measured in 6 slices, and regions of sub-segmental ‘hotspot’ elevation (3 continuous voxels T1&gt;1050 ms or T2&gt;60 ms) were identified. Rejection treatment was per institutional protocol, blinded to CMR results, categorized as (A)new IV therapy, (B)oral augmentation of maintenance, or (C) no change. Sensitivity, specificity and ROC analyses were performed. Results: 95 encounters in 34 patients (median age 13.1y (IQR 7.5-16.3), BSA 1.37 m2 (1.1-1.6), 47% female) were completed, with treatment groups A 13%, B 5%, and C 82%. Significantly higher T1 and T2 values were found in the rejection groups. ROC curve analysis identified elevated peak T1 levels as the strongest predictor of rejection (AUC = 0.848, 95% CI: 0.746, 0.950, p&lt;0.001), with optimal cutoff T1 &gt;1099 ms. Subsegmental hotspots were present in all encounters with rejection requiring new therapy (100% sensitivity), however the type/ number of hotspots did not correlate with rejection. New rejection therapy was not initiated in any patient encounter without hotspots (NPV 100%). Conclusions: Elevated segmental T1 CMR values can identify children with graft rejection, and absence of subsegmental hotspot elevations can reliably identify patients without rejection. CMR is a promising non-invasive test to aid in graft surveillance and direct invasive testing and therapy.
Abstract 4141090: Implications of Tricuspid Regurgitation Severity in Patients Undergoing Mitral Transcatheter Edge-to-Edge Repair
Authors: Alon Shechter, HOMA TAHERI, TAKASHI NAGASAKA, Aakriti Gupta, Danon Kaewkes, Vivek Patel, Kazuki Suruga, Manvir Dhillon, Keita Koseki, Ofir Koren, Moody Makar, Sabah Skaf, Dhairya Patel, Tarun Chakravarty, Raj Makkar, Robert Siegel
Journal: Circulation (2024)

Background– Prognostically-meaningful tricuspid regurgitation (TR) surrounding transcatheter edge-to-edge repair (TEER) for mitral regurgitation (MR) is ill-defined. Objective– To explore the prevalence, correlates, and consequences of TR grades and postprocedural trends among mitral TEER patients. Methods– This is a single-center, retrospective analysis of isolated, first-time interventions. Pre-, intra-, and post-procedural aspects up to 1-year, of them the primary composite outcome of all-cause deaths or heart failure (HF) hospitalizations, were assessed according to continuous/categorical TR severity at baseline and 1-month post-TEER. Results– Overall, 1,287 individuals (60.3% males, age 78 (IQR, 69-85) years, 52.9% with functional MR) were included. Below-moderate, moderate, and above-moderate TR affected 48.4%, 29.5%, and 22.1% of patients, respectively. Increasing TR severity was accompanied by higher rates of functional, severe MR, greater comorbidity, and more advanced HF. Although not affecting technical and echocardiographic procedural success, moderate-and-above TR degrees were associated with higher incidence of mortality, HF admissions, and functional class III-IV post-procedure, with moderate-to-severe and greater TR independently conferring increased risks for the various outcomes (primary endpoint – HR 1.36, 95% CI 1.21-1.80, p=0.027). One-month postprocedural TR severity directly correlated with and was generally similar to or worse than its baseline counterpart. Rather than the direction/magnitude of change between the two, moderate-and-above grade at 1-month, observed in 37.1% of eligible patients, emerged as predictive of the primary outcome’s risk. Conclusion– Among mitral TEER patients, above-moderate TR at baseline and the closely-related moderate-and-above TR at 1-month post-procedure are highly prevalent and signal suboptimal outcomes. The potential benefit of simultaneously addressing such significant TR at the time of mitral TEER warrants further investigation.
Abstract 4141392: The LDL-C Lowering Effect and Patient Out-of-Pocket Cost Among Patients Who Received Inclisiran Treatment at Outpatient Clinics
Authors: Nihar Desai, Nicholas Van Hise, Xiaoli Niu, Elizabeth Ghera, Alan Brown
Journal: Circulation (2024)

Introduction: Inclisiran is a novel small interfering RNA indicated to reduce LDL-C as an adjunct to diet and statin therapy for the treatment of adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH). It is administered subcutaneously initially, again at 3 months, and then every six months by an HCP. Subsequent doses may be administered within three months after the scheduled dose without restarting a new dose schedule. Few studies have investigated out of pocket (OOP) costs for patients receiving inclisiran. Metro Infusion Center (MIC) is one of the largest infusion centers across the US with over 200 centers in 38 states. Objective: To describe the real-world changes in LDL-C levels and OOP costs associated with inclisiran use at MICs. Methods: Patient charts for those who initiated inclisiran between March 1, 2022 and November 30, 2022 and who received ≥2 doses were reviewed retrospectively. Patient characteristics at initiation were collected and patients were followed until February 2024. Study outcomes included changes in LDL-C levels from baseline and OOP cost by payer type. The incidence of adverse events (AEs) was extracted from the chart if documented. Results: A total of 534 patients who initiated inclisiran received ≥2 doses. Mean (SD) age was 70.2 (10.3) years and 50% were male. The majority of patients (81%) were covered by Medicare. A total of 479 (90%) patients had a history of ASCVD and 55 (10%) had HeFH. Prior PCSK9i use was reported in 35% of patients, and 54% had concurrent statin therapy. Among 274 patients with LDL-C measurements, mean (SD) baseline LDL-C was 147.2 (59.7) mg/dL. After initiating inclisiran, the average reduction in LDL-C from baseline was 47%. The average OOP costs for the initial dose was $37 ($0-$2950) for Medicare insured patients and $115 ($0-$1300) for patients covered by commercial insurance. Among patients insured by Medicare, 96% paid $0 OOP for both doses. A total of 24 (4%) patients reported an AE, and half discontinued treatment. The most commonly reported AEs were muscle weakness and joint pain in 5 patients. Conclusion: These real-world data demonstrate significant LDL-C reductions within 1 year in patients who initiated inclisiran, which is consistent with the ORION clinical development program. Most patients were covered by Medicare, nearly all of whom had $0 for OOP costs compared with average costs of $115 for initial dose for commercially insured patients.
Abstract 4140883: Human iPSCs and Human iPSC-Endothelial cells Derived from PAD Patients and Healthy Donors Have Similar Characteristics and Potency: Implications for Autologous Cell Therapy in Peripheral Artery Disease
Authors: Jung Yoon Bae, Shin-Jeong Lee, Seongho Bae, Cholomi Jung, Ji-Hyeon Jung, Ji Woong Han, Sin-Hye Park, Yonghak Kim, Jungwoo Kim, Hyun-Kyung Kim, Seung-Jun Lee, Young-Guk Ko, Donghoon Choi, Hyun Ok Kim, Young-sup Yoon
Journal: Circulation (2024)

Background: Peripheral artery disease (PAD) can lead to amputation in advanced cases, making cell therapy using human induced pluripotent stem cells (hiPSCs) a promising therapeutic option. hiPSC-derived endothelial cells (hiPSC-ECs) have shown favorable effects in treating experimental ischemic cardiovascular disease. An autologous approach for PAD patients is preferable to avoid immunological reactions. However, it is yet unknown whether hiPSCs and hiPSC-ECs derived from PAD patients have similar characteristics and potency compared to those derived from healthy volunteers. Therefore, we explored whether there are significant differences in the characteristics and potency of hiPSCs and hiPSC-ECs between non-PAD donors and PAD patients. Methods and Results: We successfully generated hiPSCs from the blood of seven non-PAD donors and eight PAD patients. Both non-PAD and PAD-derived hiPSCs exhibited similar expression levels of pluripotency markers, as determined by qRT-PCR, flow cytometry, and immunostaining. All hiPSCs, regardless of the group, formed teratomas and showed normal karyotypes. RNA-seq analyses revealed similar gene expression profiles between the groups. We then differentiated hiPSCs into endothelial cells (ECs) in a clinically compatible manner. hiPSC-ECs derived from both non-PAD and PAD donors exhibited similar expression levels of EC markers at both the gene (qRT-PCR) and protein levels (immunostaining and flow cytometry). RNA-seq analyses showed no significant overall differences in gene expression profiles between the groups. In vitro nitric oxide assays and tubular structure formation assays demonstrated similar endothelial characteristics and function in hiPSC-ECs from both groups. When injected into the hindlimb muscle following induction of hindlimb ischemia, both groups showed similar perfusion recovery, limb salvage, and vessel-forming capacity. Engrafted hiPSC-ECs from both groups also exhibited similar angiogenic and vessel-forming capabilities. Conclusions: Our study demonstrated no significant differences in hiPSCs and hiPSC-ECs derived from non-PAD donors and PAD patients in terms of molecular and cell biological characteristics, therapeutic effects, and vessel-forming capability. Our study indicates that hiPSCs and hiPSC-ECs derived from PAD patients can serve as a novel platform for autologous cell therapy.
Abstract 4141007: Incidence of positive cardiac positron emission tomography in genotype-positive patients: A Cardiovascular Genetics Clinic lens
Authors: Kathleen Trinh, Jessica Wang
Journal: Circulation (2024)

Background: Positron emission tomography-computed tomography (PET-CT) is widely used to diagnose cardiac sarcoidosis (CS) for treatment. There is increasing recognition of myocardial inflammation in genetic arrhythmogenic cardiomyopathy (ACM) masquerading as CS. Since our institution is a high-volume arrhythmia center that frequently utilizes cardiac PET-CT studies to assess for CS and genetic evaluation to diagnose genetic cardiomyopathy (GNC), our clinical cohort is enriched for patients with both studies. Research Question: We hypothesize cardiac PET positivity is a unique feature of ACM among GNC, accompanied by markers of myocardial injury and improvement after anti-inflammatory therapy. (Steroids currently do not play a role in ACM treatment.) Goals: This investigation seeks to delineate the potential role of PET-CT and anti-inflammatory therapy in ACM. Methods: All UCLA Cardiovascular Genetics Clinic patients who underwent a cardiomyopathy gene panel were included. Patient genotypes were classified as positive – harboring at least a pathogenic (P) or likely pathogenic (LP) variant, uncertain – at least a variant of uncertain significance, or negative. Genes were grouped into ACM or non-ACM based on the 2019 Heart Rhythm Society consensus. Patients were screened for PET-CT scans before genetic testing. PET-CT positivity was defined by cardiac FDG uptake without extracardiac uptake. Results: Forty-eight patients received a PET-CT scan, with 58% (28/48) harboring a positive genotype. Of 320 patients with P/LP variants, 28 (8.8%) underwent PET-CT scans (11 ACM, 17 non-ACM). Six scans were positive, including 3 ACM genes. PET-CT positivity rates were 27.3% (3/11) for P/LP ACM genes and 17.6% (3/17) for P/LP non-ACM genes. Among the 6 PET-CT-positive patients, 3 ( FLNC , GAA , MYH7 ) received immunosuppressive therapy with variable response. Our FLNC patient showed no improvement after 6 months of steroids. Conclusion: We recommend genetic testing for suspected CS cases with positive cardiac PET-CT without extracardiac manifestation. Cardiac PET-CT positivity led to a high genetic diagnostic yield (58%) in our clinic, where the genetic finding was enriched for but not limited to ACM gene mutations. Our limited sample of steroid treatment yielded varied results. A consortium approach to delineate patient characteristics, immunosuppressive responsiveness, and randomized control trials may help address these knowledge gaps in the future.