bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4140102: Changes in EQ-5D-5L with Aficamten in Obstructive Hypertrophic Cardiomyopathy (oHCM): the SEQUOIA-HCM Trial
Authors: Schulze Christian , Abraham Theodore , Barriales-Villa Roberto , Claggett Brian , Coats Caroline , Garcia-Pavia Pablo , Hagege Albert , Januzzi James , Kulac Ian , Kwong Raymond , maron Martin , Masri Ahmad , Nassif Michael , Olivotto Iacopo , Spertus John , Veselka Josef , Butzner Michael , Heitner Stephen , Jacoby Daniel , Kupfer Stuart , Malik Fady , Meng Lixin , Shreay Sanatan , Wohltman Amy , Maurer Mathew
Published: November 2024

Introduction:
In patients with obstructive hypertrophic cardiomyopathy (oHCM), the SEQUOIA-HCM trial demonstrated that aficamten, a next-in-class cardiac myosin inhibitor, improved exercise capacity, heart failure symptoms and hemodynamics compared with placebo. Aficamten’s impact on overall quality-of-life (QoL) in oHCM has not been reported.

Hypothesis:
Aficamten, compared with placebo, improves QoL as assessed by the EQ-5D-5L.

Aims:
To describe EQ-5D-5L changes in patients enrolled in SEQUOIA-HCM.

Methods:
SEQUOIA-HCM (NCT05186818) is a phase III, placebo-controlled trial of adults with symptomatic oHCM randomized to aficamten (n=142) or placebo (n=140) on top of standard-of-care medical therapy. Participants underwent blinded dose escalation over 6 weeks and were treated for 24 weeks followed by a 4-week washout. EQ-5D-5L (ranges from 0 to 1) and overall QoL using the Visual Analogue Scale (VAS; from 0 to 100) was measured at baseline through week 28 with higher scores indicating better QoL. Aficamten treatment effect on EQ-5D-5L was estimated using linear regression (study visits) and mixed effects regression (overall treatment effect) using all follow-up data with model adjustments for baseline EQ-5D-5L score and randomization stratification variables.

Results:
Mean age (n=282) was 59.1±12.9 years (40.8% women; 79.1% white). Aficamten baseline EQ-5D-5L index and VAS scores were 0.8±0.19 and 71.2±17.9 (placebo: 0.78±0.2; 68.9±18.6), respectively. Aficamten improved the EQ-5D-5L by 0.026 (95% CI: -0.001, 0.052; p=0.056) and the VAS by 2.8 points (95% CI: 0.8, 4.8; p=0.006) versus placebo with significant differences as early as 8 weeks after treatment initiation (p=0.005). After treatment withdrawal at 24 weeks, QoL benefits in aficamten-treated patients decreased compared with placebo (Figure: Index, p<0.001; VAS, p=0.003), with hemodynamic parameters returning to baseline.

Conclusions:
Aficamten yielded early, sustained and significant improvement in overall QoL compared with placebo. Withdrawal of aficamten was associated with the loss of treatment benefits and perhaps an increased perception of pre-treatment symptoms. These data support a role of aficamten in improving QoL among patients with oHCM.
Abstract 4140118: Identification of Obstructive and Non-Obstructive Hypertrophic Cardiomyopathy Patients Using Natural Language Processing in a Large Integrated Healthcare System
Authors: Sheridan Ann , Liu Jane , Tabada Grace , Tan Thida , Dubey Anand , Lucas Matthew , Zhong Yue , Okano Gary , Solomon Matthew
Published: November 2024

Introduction:
Accurately identifying and characterizing patients with hypertrophic cardiomyopathy (HCM) is critical for population management and care optimization.

Research Question:
To develop natural language processing (NLP) algorithms to identify and characterize obstructive (oHCM) and non-obstructive (nHCM) HCM patients directly from echocardiograms, and to compare with the presence or absence of HCM-related diagnosis codes.

Methods:
We developed and validated NLP algorithms to identify HCM from all adult (age≥18yrs) echocardiograms performed from 2010-2019 in Kaiser Permanente Northern CA (KPNC), capturing measures of any HCM, HCM subtype, hypertrophy subtype, septal and posterior LV wall thickness, resting and stress/Valsalva LVOT gradients, and systolic anterior motion. We developed a rules-based algorithm (following AHA/ACC criteria) to classify patients as having HCM, including oHCM or nHCM subtypes, and possible HCM (defined as wall thickness ≥2cm without other criteria meeting an HCM definition). We evaluated the presence of HCM-related ICD-9/10 diagnosis codes among patients classified as HCM/non-HCM from echocardiograms using NLP, and linked baseline demographics and clinical parameters from our integrated electronic medical record.

Results:
Among 472,405 adults with echocardiograms, we identified 2,892 patients with HCM based upon NLP-derived measures (all NLP measures achieved >95% positive predictive value and >95% negative predictive value), including 1,585 (55%) with oHCM, 1,145 (40%) with nHCM, and 162 (6%) which could not be classified (Figure). Among those 2,892 patients, 1,283 did not have any associated HCM ICD-9/10 diagnosis codes (Table). Among 469,513 patients with no identified HCM from NLP-based algorithms, HCM ICD-9/10 diagnosis codes existed in 1,567 patients (Table). We also identified 4,593 patients with possible HCM by NLP, only 4.5% of whom had an associated HCM code. Among confirmed HCM patients by NLP, oHCM patients were slightly older (66 vs 61 yrs), more likely female (53% vs 43%), had similar mean septal wall thickness (1.7cm vs 1.7cm), but were more likely to have a septal hypertrophy subtype (46% vs 28%) compared to nHCM patients.

Conclusions:
Echocardiogram-based NLP methods can improve the identification of and care for HCM patients. Many patients with possible HCM may be underdiagnosed, representing an opportunity for quality improvement.
Abstract 4140130: Association of Depression and Anxiety with Coronary Plaque: The Miami Heart Study (MiHeart)
Authors: Bafna Tanvi , Dzaye Omar , Dardari Zeina , Cainzos Miguel , Blankstein Ron , Feldman Theodore , Budoff Matthew , Fialkow Jonathan , Nasir Khurram , Blaha Michael
Published: November 2024

Introduction:
The prevalence of psychological disorders have been increasing, especially since the COVID-19 pandemic. Multiple mechanisms such as medication nonadherence, negative coping behaviors, and systemic inflammation may mediate the potential effects of depression and anxiety on atherosclerosis.

Question:
Is there an association of depression or anxiety with the presence of plaque assessed by coronary computed tomography angiography (CCTA) among adults free of clinical coronary artery disease (CAD)?

Aim:
We aim to examine the association of psychological factors with CCTA-based plaque, as they may be key targets for prevention and CCTA could be considered for enhanced risk characterization.

Methods:
This cross-sectional study analyzed baseline data from the community-based Miami Heart Study (MiHeart). Depression was assessed by the Patient Health Questionnaire 8-item scale with a score ≥10 indicating binary depression. Anxiety was assessed by the Generalized Anxiety Disorder 7-item questionnaire with a score ≥10 demonstrating binary anxiety. The outcome was the binary presence of any plaque on CCTA. Multivariable logistic regression models were adjusted for potential confounders and clinically relevant risk factors. Sensitivity analyses further examined the severity of depressive symptoms, severity of anxiety symptoms, individuals with either depression or anxiety, and individuals with both depression and anxiety as predictors of coronary plaque.

Results:
Of the 2,356 individuals (mean age 53.4±6.8 years), 50.4% were men and 47.1% were of Hispanic ethnicity. Depression and anxiety were reported in 143 (6.1%) and 224 (9.5%) of individuals, respectively. CCTA-identified plaque was present in 49.0% of participants with depression and 54.0% of those with anxiety, and plaque presence did not significantly differ when compared to those without depression or without anxiety, respectively. There were no significant associations between depression and plaque (adjusted odds ratio [aOR]: 1.03; 95%CI [0.70, 1.52]; p=0.891) or between anxiety and plaque (aOR: 1.27; 95%CI [0.93, 1.73]; p=0.138) in all regression models. On sensitivity analysis, there were also no statistically significant associations found.

Conclusion:
Our study found no association of depression, anxiety, their combination, or their severity with coronary plaque on CCTA in asymptomatic adults. To our knowledge, this is the first large study on this topic utilizing CCTA data in a U.S. population.
Abstract 4140138: Coronary Artery Vasculopathy in a Cohort of 321 Heart Transplant Recipients: A Single Center Experience
Authors: Krayem Hussein , Cooke Richard , Abouzaki Nayef , Kutkut Issa
Published: November 2024

Introduction:
Despite advances in surgical techniques, organ preservation methods and immunosuppressant medications, the ten-year survival for orthotropic heart transplantation (OHT) remains around 50%. Coronary artery vasculopathy (CAV), among other factors, seems to have an important role in accelerated organ injury and failure.

Aim:
To determine the rate of survival and CAV development along with associated factors in a cohort of OHT recipients.

Methods:
Patients who underwent OHT at Virginia Commonwealth University (VCU) between October 2008 and September 2021 were retrospectively reviewed until June 2024. According to the VCU protocol, right heart biopsies were done weekly for the first month, every other week for the second month and at the first year mark post transplant. Left heart catheterizations were done one year after OHT and then at 2 year intervals. Survival, CAV development and need for percutaneous coronary interventions (PCI) as well as organ rejection rates in CAV patients were surveyed.

Results:
A total of 321 patients received OHT during that period with a median follow up time of 8.15 years from the date of transplant. Of these, 122 patients had 10-year follow up or more post OHT (53.27% survived) and 240 patients had 5-year follow up or more (66.25% survived). All patients had greater than 2.75 years of follow up. The overall mortality was 29.5%. CAV occurred in 55 patients out of 321 (17%) with median time of 2.82 years for CAV development. Mortality in the CAV group was 40% compared to 27% in the non-CAV group. Out of 55 patients with CAV, 19 required at least 1 PCI with 3 requiring interventions on chronic total occlusions. Evidence of rejection on right ventricle biopsy was observed in 51% of patients with CAV

Conclusion:
Our cohort had above average 10-year survival rate compared to the national data. Results revealed CAV is common post OHT and has implications on long term survival. Given CAV may develop in the absence of organ rejection, further studies are needed to identify factors associated with CAV and explore optimal treatment options that would potentially improve long-term survival post OHT.
Abstract 4140149: Differences in Interventional Treatment Outcomes of Peripheral Arterial Disease between African American Females, African American Males, and Caucasian Females
Authors: Lurie Fedor , Oriowo Babatunde , Russell Todd , Hallett Kelly , Kasper Gregory
Published: November 2024

Introduction:
Several recent publications demonstrated worse outcomes of interventional treatment of peripheral arterial disease (PAD) in patients of African American (AA) descent compared to Caucasians (C), and in female patients compared to male patients. However, studies addressing sex differences in outcomes, included predominantly white female patients. To our knowledge, there are no published studies specifically addressing outcomes of interventional treatment of PAD in female patients of African American descent.

Aims:
1. To determine if the outcomes of interventional treatment of PAD in female patients of African American (FAA) descent differ from male African American patients (MAA), and Caucasian female patients (FC). If such differences exist, to identify factors associated with it.

Methods:
This study has a cross-sectional design with systematically retrospective data collection by the National Vascular Quality Initiative. Included in this study was data on patients treated with endovascular and open surgical options for symptomatic PAD. Statistical analysis was done using IBM Statistic SPSS V25.

Results:
447,263 unique cases containing required data were available in the VQI database. Among them, 171,250 were female patients, of which 32,966 were FAA, 126,519 FC, and 39,461 MAA. This race and gender distribution is not significantly different from the US population structure (US Census Bureau 2023).
1
However, female to male ratio was higher in AA (0.83) compared to C (0.58, p<0.0001). FAA were younger (65.143+/-9.59) compared to FC (69.16+/-10.32, P<0.00001). Comparison of comorbidities, smoking rates, pre-interventional medications and post-interventional outcomes are listed in Table 1. Multivariate analysis confirmed higher amputation rate among FAA compared to FC and to MAA and showed no significant difference in mortality.

Conclusions:
FAA patients who require interventional treatment for PAD have significantly higher rate of hypertension and diabetes compared to FC and MAA patients and have higher amputation rates. It appears that differences in clinical outcomes of PAD treatment in FAA are related mostly if not entirely to poorly managed comorbidities existed prior to intervention.
Abstract 4140167: Lipid Management among US Veterans with Prevalent Atherosclerotic Cardiovascular Disease (ASCVD) * Veteran Affairs Lipid Optimization Reimagined Quality Improvement Program (VALOR-QI)
Authors: Leya Jeff , Hines Kyle , KALAPALA HEPSI , QUILLIAN CHRISTINA , Gutierrez Salvator , Thomas Sonia , tully marianne
Published: November 2024

ASCVD is the most prevalent form of cardiovascular disease and the main cause of morbidity and mortality for Veterans in the VA healthcare system. Management of cholesterol is one of the most effective approaches for reducing CV disease, however, over two-thirds of Veterans with ASCVD are not optimally managed. Veterans with ASCVD are at high risk for recurrent CV events and can benefit greatly from more effective management of their low-density lipoprotein (LDL-C) cholesterol. The reasons for the current undertreatment of dyslipidemia in Veterans with ASCVD are multifaceted, including factors such as low disease awareness among the patients, patient’s preference, statin intolerance, and poor adherence to medications.

Purpose:
VALOR-QI is a collaborative effort between the U.S. Department of Veterans Affairs (VA) and the American Heart Association (AHA) with the goal of positively impacting Veterans’ cardiovascular health.

Method:
This project targets at risk veterans over 18 years of age, with ASCVD and LDL-C ≥70 mg/dl or non-HDL-C ≥100 mg/dl identified across 50 VA medical centers nationwide. 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. Health coaches at these centers aid in lipid optimization through patient counseling, medication adherence support, appointment reminders, and referrals to a nutritionist or clinical pharmacist as required.

The plan’s effectiveness will be assessed by tracking LDL-C goal achievement rates, LDL-C changes with therapy use, and veteran demographics. Our primary endpoints are for over 30% of veterans to reach the LDL-C target and a significant drop (around 10%) from baseline in veterans with ASCVD and LDL-C not at target. Best practices are shared among sites using the PDSA implementation science model.

Results:
As of May 2024, 182 patients at the Hines VA are engaged in the project. Among them, 84.8% are on lipid-lowering therapy, 83.1% are on statins (with 57.9% on a high intensity dose), and 11.3% are on dual therapy with a statin plus an additional medication (PCSK9 inhibitor or ezetimibe). So far, 59.5% of enrolled patients reached their LDL-C cholesterol target of <70 mg/dl.

Conclusion:
Lipid lowering strategies with collaboration of patients, network providers, dieticians and health coaches improved lipid control in veterans with ASCVD.
Abstract 4140191: ChREBP Drives Brown Adipocyte Differentiation and Lipid Utilization for Excess Energy Expenditure
Authors: Inoue Oto , Ginugu Meghana , Singh archana , Sanchez-Gurmaches Juan
Published: November 2024

Introduction:
Although several anti-obesity drugs have become recently available, they reduce patients’ appetite, which might worsen cardiovascular disease (CVD) prognosis by malnutrition/cachexia. Brown adipose tissue (BAT) oxidizes glucose and lipids for thermogenesis, a process that requires excess energy expenditure provided by uncoupling protein 1 (UCP1)
+
cells. Recently, critical roles of BAT in cardio-protection have been discovered. Taken together, boosting BAT activity can be a novel anti-obesity treatment suitable for CVD patients. In this study, we aimed to establish anti-obesity strategy by manipulation of the glucose-sensing lipid-storage transcription factor, ChREBP, with unexpected function of boosting lipid utilization in BAT.

Methods and Results:
Through mouse/human single-cell/nucleus RNA sequencing analyses, we identified ChREBP as specifically expressed in highly thermogenic UCP1
+
brown adipocytes (
Fig.A
). To investigate the role of ChREBP in BAT formation, we generated human brown adipocyte-like model from induced pluripotent stem cells (iPSC-BAT,
Fig.B
). The iPSC-BAT exhibited high UCP1 and ChREBP expression, multi-locular lipid droplets, and vigorous oxygen consumption. Knocking down ChREBP strongly blocked iPSC-BAT differentiation (
Fig.C
) and impaired lipid utilization (
Fig.D
).

Consistently, in vitro deletion of ChREBP in mouse BAT progenitors impeded differentiation, lipid droplet accumulation, and oxygen consumption (
Fig.E-F
). In vivo, BAT-specific deletion of all ChREBP isoforms reduced lipid accumulation and BAT characteristics. Conversely, using a new mouse model for Cre-mediated ChREBPβ overexpression, we showed that ChREBPβ overexpression in BAT (Chβ BATOX) increased BAT cellularity and activated lipogenic machineries, with paradoxical decreased lipid content, suggesting excessively activated lipid consumption in BAT (
Fig.G
). More importantly, Chβ BATOX maintained UCP1 expression and reduced fat volume (
Fig.H
) even after strongly inhibiting BAT activity.

Conclusion:
In summary, ChREBP is essential for BAT development and thermogenic capacity by affecting lipid utilization. Our results suggest that ChREBPβ activation may be a novel anti-obesity avenue for CVD patients.
Abstract 4140192: Time Trends in Outcomes of Trans-Catheter Aortic Valve Replacement with Balloon-expanding Versus Self-expanding Valves: A Meta-analysis of Randomized Controlled Trials
Authors: Tavakoli Kiarash , hosseini mohammadi negin sadat , Bahiraie Pegah , Saeidi Sahar , Shaker Farhad , Soltani Moghadam Arman , Montazeri Namin Sara , Rahban Habib , Pawar Shubhadarshini , Tajdini Masih , Soleimani Hamidreza , Jenab: Cardiology In Practice Yaser , Makkar Raj , Nanna Michael , Iskander Fady , Alkhouli Mohamad Adnan , Gupta Aakriti , Hosseini Kaveh
Published: November 2024

Background:
The research on the outcomes of transcatheter aortic valve replacement with balloon-expandable valves (BEV) and self-expanding valves (SEV) are limited.

Hypothesis:
This study aims to compare the clinical and hemodynamic outcomes of BEV and SEV at short-term (30 days), mid-term (1 year), and long-term (>1 year) endpoints.

Methods:
PubMed, Embase, Scopus, and Cochrane Library databases were searched up to April 25, 2024, for randomized controlled trials (RCTs). Random-effect model (DerSimonian–Laird method) was used to pool the risk ratios (RR), mean differences (MD) and 95% confidence interval (CI) for binary and continuous outcomes, respectively.

Results:
A total of 11 RCTs comprising 4,325 patients (2,295 BEV, 2,030 SEV) were included. At short-term, the risk of cardiovascular (RR: 0.56, 95% CI: 0.36-0.87) and all-cause mortality (RR: 0.54, 95% CI: 0.35-0.81) were lower in the BEV group. However, no differences were noted between the two treatment modalities in longer follow-ups despite the lower risk of moderate to severe paravalvular leak (PVL) among BEV patients. The risk of stroke was comparable between two groups across all three follow-up endpoints, albeit a limited number of studies suggesting the BEV group showed a greater risk of clinical valve thrombosis in mid-term and long-term assessments. The need for permanent pacemaker implantation was lower in BEV arm in short-term (RR: 0.56, 95% CI: 0.37-0.87) and mid-term (RR: 0.78, 95% CI: 0.64-0.94). Yet, this difference was not observed in long-term follow-ups. Conversely, the SEV group had a larger effective orifice area with lower mean transvalvular pressure gradient from short-term (MD: 0.17, 95% CI: 0.07-0.26 and MD: 3.71, 95% CI: 2.64-4.78, respectively) to long-term (MD: 0.25, 95% CI: 0.17-0.32 and MD: 3.73, 95% CI: 3.19-4.27, respectively) periods.

Conclusions:
BEV is associated with reduced risk of clinical outcomes at short-term; however, most differences diminish in longer evaluations, except for moderate to severe PVL. Conversely, SEV is linked to better hemodynamic outcomes and a lower risk of clinical valve thrombosis across all follow-up durations.
Abstract 4141446: Sodium Glucose Co-transporter 2 (SGLT2) Inhibitors Promote Resiliency to High Pressure Stress in the Human Microvasculature
Authors: SenthilKumar Gopika , Freed Julie , Cohen Katie
Published: November 2024

Emerging evidence suggests that vascular stress from cardiovascular-related co-morbidities promotes microvascular dysfunction, a key component in the development of heart failure with preserved ejection fraction. The sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin has been shown to reduce both morbidity and mortality associated with heart failure with preserved ejection fraction, however the full scope of influence of this therapy on human microvascular function remains unknown. We hypothesized that pre-treatment of isolated human microvessels with empagliflozin will prevent stress-induced endothelial dysfunction as evidenced by preserving both the magnitude of flow-induced dilation (FID) as well as the ability to dilate to nitric oxide. Human resistance arterioles (80-250µm) from healthy adults (defined as patients with ≤1 risk factor for cardiovascular disease) were dissected from discarded surgical adipose tissue and treated with empagliflozin (1µM), or vehicle control (ethanol) for 16-20 hours prior to the flow experiment. Vessels were cannulated for videomicroscopy and subjected to high intraluminal pressure (150mmHg, 30 min), an acute stress known to induce endothelial dysfunction. Vessels were pre-constricted with endothelin-1 prior to initiation of flow. A nonlinear logistic regression was used to determine differences between curves. Compared to vehicle control, vessels pre-treated with empagliflozin (1µM ) exhibited nitric oxide-dependent FID as dilation was impaired in the presence of the nitric oxide synthase inhibitor L-NAME (EC50 Control: 10.7 vs L-NAME 83.45, p=0.0107). This data suggests that empagliflozin, an SGLT2 inhibitor, promotes microvascular resilience to stress via preservation of nitric oxide-mediated FID. The ability to elicit stress resilience may explain in part some of the cardiovascular benefits associated with SGLT2 inhibitors and may offer unique opportunities for early intervention or prevention of microvascular dysfunction associated with comorbidities that contribute to heart failure with preserved ejection fraction.
Abstract 4141460: Exploring Novel Data-Driven Clustering Methods for Uncovering Patterns in Longitudinal Neonatal Postoperative Temperature Measurements
Authors: Helman Stephanie , Riek Nathan , Sereika Susan , Olsen Robert , Gaynor J , Lisanti Amy , Al-Zaiti Salah
Published: November 2024

Introduction:
Neonatal hypothermia (< 36.5
o
C) after CPB is considered benign despite lack of evidence on its prognostic significance.

Question:
Are group-based trajectory modeling (GBTM), k-means, and self-organizing map (SOM) clustering approaches clinically useful for evaluating their associations with important outcomes?

Aims:
Identify distinct postoperative temperature trajectories in neonates after CPB using novel machine learning (ML) clustering methods, corroborate findings, and evaluate prognostic value on outcomes.

Methods:
Secondary cohort analysis of prospectively collected data. Accessed data from a single pediatric referral center's CardioAccess registry consistent of postoperative neonates with congenital heart defects (CHD). 48-hourly postoperative temperature measurements were extracted from patient records. GBTM, SOM, and k-means clustering identified cluster membership and model fit was optimized for 3 clusters based on existing knowledge. The primary outcome was a complication composite of severe bleeding, illness severity, cardiac arrest, arrhythmia, delayed first successful extubation, prolonged ICU LOS, very poor weight gain, and 30-day mortality. 3 data driven techniques were compared and then associated with outcomes using adjusted multivariable binary logistic regression (LR).

Results:
450 neonates ≥ 34 weeks gestation undergoing CPB between 2015 and 2019 met inclusion criteria. GBTM, SOM, and k-means clustering identified temperature group assignment for 3 clusters: 1) persistent hypothermia (n=38, 9% vs. n=49, 11% vs. n=40, 9%), 2) resolving hypothermia (n=233, 51% vs. n=227, 50% vs. n=147, 33%), and 3) normothermia (n=179, 40% vs. n=174, 39% vs. n=263, 58%). Concordance of techniques showed strong agreement between GBTM and SOM (kappa= 0.92). The kappa test comparing GBTM and k-means assignment was 0.41, indicating a weak to moderate agreement. After adjustment in the multivariable binary LR, persistently hypothermic neonates compared to normothermic neonates were associated with higher odds of the complication composite outcome in the GBTM (OR: 2.8 [1.0-7.3], p 0.041) and SOM (OR: 2.3 [1.0-5.4], p 0.045) models, but not the k-means model (OR: 1.4 [0.7-3.1], p 0.38).

Conclusion:
Exploring concordance between different unsupervised ML techniques, shows that neonatal temperature after CPB follows distinct postoperative trajectories, and those exhibiting a persistent hypothermia trend are at higher risk of adverse outcomes.
Abstract 4141487: Social Determinants of Health and Outcomes in Patients with Hypertrophic Cardiomyopathy in the Sarcomeric Human Cardiomyopathy Registry (SHaRe)
Authors: Hafeez Neha , Claggett Brian , Owens Anjali , Helms Adam , Saberi Sara , Lampert Rachel , Stendahl John , Ashley Euan , Parikh Victoria , Lakdawala Neal , Ingles Jodie , Olivotto Iacopo , Ho Carolyn , Taylor Matthew , Khan Sadiya , Day Sharlene
Published: November 2024

Introduction:
Area-based social determinants of health (SDOH) are associated with higher risk for acquired heart disease. However, the impact of area-based SDOH on clinical outcomes in patients with hypertrophic cardiomyopathy (HCM) has not been previously studied.

Hypothesis:
Residing in an area with lower median household income and a higher social deprivation index (SDI) are independently associated with adverse outcomes in patients with HCM.

Methods:
This study included 4,483 adult patients with HCM from five Sarcomeric Human Cardiomyopathy Registry (a multi-center prospective registry of patients with HCM) sites in the US followed for a median [IQR] of 4.0 [1.0-8.5] years. The patients’ residential address was geocoded at the zip code level to characterize median household income and SDI. SDI is based on various social factors (such as income and education), with a higher score reflecting more deprivation. Multivariate models, adjusting for sex, age, hypertension and body mass index were used to determine the independent association of household income and SDI on ventricular arrhythmias (VA), heart failure (HF), and an overall composite outcome (VA, HF, atrial fibrillation, death, and stroke).

Results:
Median age at diagnosis was 48.3 [32.0-60.4] years with 42.0% female. Median household income was $90,000 [60,000-110,000] and median SDI was 25 [10-55]. Adjusted hazard ratios per $10,000 higher income were 0.96 (95% CI 0.93-1.00, p=0.03) for VA, 0.91 (95% CI 0.90-0.93, p <0.01) for HF, and 0.95 (95% CI 0.94-0.96, p <0.01) for the composite outcome. Adjusted hazard ratios per 10 units higher SDI (more deprived) were 1.07 (95% CI 1.03-1.12, p<0.01) for VA, 1.06 (95% CI 1.04-1.08, p <0.01) for HF, and 1.05 (95% CI 1.03-1.06, p <0.01) for the composite outcome. The associations of SDI and income on clinical outcomes were similar regardless of sarcomere gene variant status.

Conclusions:
Residing in an area with lower median household income and higher SDI were independently associated with adverse outcomes in patients with HCM. These findings extend observations from acquired cardiovascular disease and highlight the need to address adverse SDOH to reduce health disparities and improve outcomes in patients with HCM.
Abstract 4143220: Racial Differences in Prescription of SGLT2 Inhibitors and GLP1 Receptor Agonists Among US Veterans with Type 2 Diabetes and Coronary Artery Disease
Authors: Bolden Demetria
Published: November 2024

Background:
Clinical trials have demonstrated that sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) reduce cardiovascular (CV) risk in patients (pts) with type 2 diabetes (T2D) with or at high risk for CV disease. Adoption of new therapies has often lagged for Black pts compared with non-Hispanic White pts, contributing to poorer health outcomes.

Methods:
We identified Veterans with T2D and angiographic CAD between 2015 and 2020 at 84 Veterans Affairs (VA) medical centers who met eligibility criteria for the EMPA-REG OUTCOME or LEADER trials that first established the clinical efficacy of SGLT2i and GLP1RA, respectively. Within each cohort (SGLT2i- and GLP1RA-eligible), we used multivariable logistic regression adjusted for demographic and clinical covariates to estimate associations of race with evidence-based drug prescription. We evaluated patterns of evidence-based prescription of SGLT2i and GLP1RA over time and by race in US Veterans with T2D and coronary artery disease (CAD).

Results:
Of 63,561 pts with T2D and CAD, 3,527 Black and 18,668 White pts met trial eligibility criteria for SGLT2i treatment and 2,020 Black and 10,103 White pts for GLP1RA treatment. Evidence-based prescription of both classes increased over time for both races (
Figure
) but reached only approximately 40% for SGLT2i and 15% for GLP1RA in 2023. For SGLT2i, race (Black/White) was not associated with evidence-based prescription (adjusted odds ratio [OR] 0.96, 95% CI 0.89-1.04, P=0.3). However, Black pts were less likely than White pts to receive evidence-based prescription of GLP1RA (adjusted OR 0.85, 95% CI 0.74-0.98, P=0.025).

Conclusions:
Among pts with T2D and CAD in the VA healthcare system, evidence-based prescription of SGLT2i and GLP1RA increased over time, but many eligible pts remained untreated. Prescription of SGLT2i did not differ by race, but Black pts were less likely than White pts to have evidence-based prescription of a GLP1RA. Disparities in evidence-based use of CV treatments may be specific to certain drug classes, even in a healthcare system with few economic barriers. Further investigation is needed to determine underlying causes and solutions for such disparities.
Abstract 4143242: Right Ventricular Remodeling During the First Decade After Tetralogy of Fallot Repair: An Echocardiographic Study
Authors: Galan Jose , Jones Andrea , Numata Ryusuke , Mondal Antara , Thomas Angeli , Wang Yan , DiLorenzo Michael , Zavez Alexis , Goldmuntz Elizabeth , Mercer-Rosa Laura
Published: November 2024

Background:
After TOF repair (TOFr), pulmonary regurgitation resulting in right ventricular (RV) dilatation and dysfunction is common. We have previously demonstrated that RV function (RVF) improves in the first two years after TOFr, however RV changes in the first decade after TOFr are less known. We investigated RVF and RV size (termed remodeling) using echocardiography during the first decade after TOFr.

Methods:
Retrospective cohort study of patients who underwent TOFr and were followed at our institution from 3/2012 to 12/2023. Those with at least two echocardiograms separated by one year were included. Two patients that received a pulmonary valve replacement were excluded. After confirming intra- and inter-reader reproducibility, RV remodeling was assessed offline by global longitudinal strain (GLS), free wall strain (FWS), fractional area change (FAC), end systolic area (ESA/BSA) and end diastolic area (EDA/BSA). RVF changes over time were assessed with multivariable linear mixed effects models adjusting for perioperative covariates. Two years after TOFr (Y2) was used as reference given RVF peaks at this point following surgery.

Results:
Out of 758 echocardiograms from 116 patients, 688 were suitable for analysis. Median age at TOFr was 3.5 months (IQR:1.92, 4.89). Compared to Y2, we identified the largest decline in RVF at Year 3, with no worsening from year to year until Y10. There were no associations of perioperative covariates with RVF except for ventriculotomy (FAC) and residual pulmonary stenosis (FWS). There was no progression in RV remodeling over the first decade after TOFr. (Graph, table).

Conclusion:
After the initial 2-year improvement following TOFr, RVF worsens but remains stable throughout the first decade with stable RV size accounting for BSA. Our findings augment the knowledge of RV remodeling during childhood and could help guide outpatient follow up, counseling, frequency of echocardiograms, and timing of the first cardiac MR.
Abstract 4144560: Phase 2 Open-label, Single-arm, Multi-center Clinical Trial to Evaluate the Efficacy and Safety of Camostat Mesylate in Patients with Protein-losing Enteropathy after Fontan Operation-Preliminary Outcome
Authors: Park Woo Young , Kim Gi Beom , Lee Sang , Baek Jae Suk , Kim Soo jin , Jung Jowon , Hyun Myung Chul , Lim Young Tae , Lee Hyoung-Doo , Ko Hoon , Lee Joowon
Published: November 2024

Introduction:
Protein-losing enteropathy (PLE) is a multifaceted condition that profoundly affects the systemic health and quality of life of Fontan patients. Despite medical progress, the treatment of PLE remains a significant challenge. This study investigates the efficacy and safety of Camostat Mesylate for managing PLE patients who have undergone the Fontan operation.

Hypothesis:
We hypothesize that Camostat Mesylate will enhance the gut environment, resulting in increase of serum albumin levels and decrease of stool alpha-1 antitrypsin levels in PLE patients following Fontan operation.

Methods:
This phase 2, multicenter, open-label, single-arm trial included patients over 4 years old diagnosed with PLE following Fontan operation. Camostat Mesylate was added to conventional treatments, with follow-up assessments at 1, 3, and 6 months, and a final evaluation one month after discontinuation. Efficacy was measured by changes in serum albumin, stool alpha-1 antitrypsin levels, and PLE symptoms such as diarrhea, edema, weight changes, and ascites.

Results:
Nineteen patients were enrolled in the study, of whom fifteen patients completed follow-up as per protocol. The median age was 15 years (interquartile range, 12.0-21.3). The median time between the Fontan operation and PLE diagnosis was 2.4 years. Serum albumin levels increased from 2.5 to 2.6 g/dL (p=0.504), and stool alpha-1 antitrypsin levels decreased significantly from 280.0 to 172.1 mg/dL (p=0.033). Notably, patients with diarrhea at baseline showed substantial improvement in both parameters, with increased serum albumin levels from 1.8 to 2.2 g/dL and decreased stool alpha-1 antitrypsin levels from 220.3 to 80.2 mg/dL. No serious adverse events were reported during study period.

Conclusions:
Camostat Mesylate demonstrated safety and efficacy, reducing stool alpha-1 antitrypsin in PLE patients after Fontan operation, especially those with diarrhea at baseline. Therefore, Camostat Mesylate could be considered as an additional treatment option for patients with PLE following Fontan operation.

Key words:
Camostat mesylate; protein-losing enteropathy; Fontan operation

Source of Funding:
This research was funded by SNUH Lee Kun-hee Child Cancer&Rare Disease Project, Republic of Korea.
Abstract 4145821: Serial Vascular Responses of Balloon-expandable Stent with Biodegradable Film-type Graft in a Rabbit Iliac Artery Dissection Model (BioGard Study)
Authors: Park Sang Min
Published: November 2024

Introduction and Background:
Arterial dissection during endovascular therapy rarely occurs but can be lethal. A significant blood volume extravasation during coronary artery interventions is related to the very high mortality (20-30%). In this hyperacute emergent clinical situation, covered stents have been considered as a primary measure to prevent further serious arterial events. A fabric-based covered graft stents yield poor clinical outcomes. To overcome these challenges, the balloon-expandable stent with biodegradable film-type graft for treating arterial dissection was invented.

Research Questions and Objectives:
A novel balloon-expandable stent with biodegradable film graft for overcoming these issues would be valid for efficacy and safety in a rabbit iliac artery dissection model.

Method and Approach:
Eighteen iliac artery dissections were induced by balloon over-inflation on angiography (Ellis type 2 or 3) and treated using the test device (3.0 x 24 mm). Subsequently, twelve animals underwent histologic examinations and micro-computed tomography (CT) at 0, 2, 4, and 8 weeks and 3, 6, 9, and 12 months and angiography at one-year.

Results and Data:
There were no adverse cardiovascular events during the one-year. Early-stage histologic examination revealed complete sealing of disrupted vessels by the device, exhibiting mural hematoma, peri-stent red thrombi, and dense infiltration of inflammatory cells. Mid- and long-term histologic examination showed patent stents with neointimal hyperplasia over the stents (% area stenosis: 11.8 at 2weeks, 26.1 at 1month, 29.7 at 3months, 49.2 at 9months, and 51.0 at 1year), along with mild peri-strut inflammatory response (Grade: 1-2 at mid-term and 0-1 at long-term). The graft film became scarcely visible after six months. Both CT and angiography revealed no instances of thrombotic occlusion or in-stent restenosis (% diameter stenosis: 5.7 at 2weeks, 12.3 at 1month, 14.2 at 3months, 25.1 at 9months, and 26.6 at 1 year).

Conclusion:
The novel balloon-expandable stent with a biodegradable film graft demonstrates feasibility in managing severe artery dissection and preventing lethal vascular events in animal model. Future human studies are warranted to validate these findings and elucidate the clinical outcomes of the study.
Abstract 4145828: The Interplay Between Exercise Load, Myocardial fibrosis, Ventricular Systolic Dysfunction and Ventricular Arrhythmias
Authors: De Paepe Jarne , D'Ambrosio Paolo , De Bosscher Ruben , Pauwels Rik , Dausin Christophe , Bekhuis Youri , Janssens Kristel , Bogaert Jan , Elliott Adrian , Ghekiere Olivier , Van De Heyning Caroline , Sanders Prashanthan , Kalman Jonathan , Fatkin Diane , Herbots Lieven , Willems Rik , Robyns Tomas , Heidbuchel Hein , La Gerche Andre , Claessen Guido
Published: November 2024

Background:
An increased prevalence of myocardial ventricular fibrosis, ventricular dysfunction and arrhythmias has been reported amongst highly trained endurance athletes, but trials investigating these adverse phenotypes in adequately sized and accurately phenotyped cohorts are largely lacking. We aimed to define the prevalence of ventricular fibrosis, ventricular systolic dysfunction, arrhythmia and their interplay in healthy endurance athletes.

Methods:
We analysed a male cohort of 244 young elite endurance athletes (20yr), 134 middle-aged recreational athletes (56yr) and 65 middle-aged non-athletic controls (55yr). CMR assessed for non-hinge point and hinge point late gadolinium enhancement (NH-LGE and H-LGE) and LVEF and RVEF. 24-hour Holter was performed to assess ventricular arrhythmia. Complex arrhythmia was defined as couplets, triplets and NSVT. Exercise load was based on questionnaires. Multiple logistic regression assessed the relationship between exercise load, LGE, ventricular systolic dysfunction and ventricular arrhythmia.

Results:
Middle-aged athletes had more NH-LGE (19.4% vs 9.2% vs 4.5%, p<0.001) and H-LGE (29.9% vs 13.8% vs 15.6%, p=0.002) than middle-aged controls and young athletes respectively. Lifetime hours of endurance exercise and age increased the odds of NH-LGE (OR 1.034, 95% CI 1.001-1.069, p=0.044 and OR 1.032, 95% CI 1.006-1.058, p=0.014). A LVEF<50% and/or RVEF<45% was more prevalent in middle-aged and young athletes compared to controls (23.1% % vs 20.5% vs 7.7%, p=0.029). A higher lifetime training load increased the odds of RVEF<45% (OR 1.059, 95% CI 1.014-1.105, p=0.009). LGE did not predict LVEF>50% or RVEF<45%.

Both complex arrhythmia and a burden of >0.1% VPB were more prevalent in middle-aged athletes compared to young athletes but not compared to controls (26.1% vs 9.8% vs 12.3%, p<0.001 and 13.6% vs 4.9% vs 7.7%, p=0.012 respectively). NH-LGE and RVEF<45% increased the odds of VPB burden >0.1%. (OR 3.845, 95% CI 1.465-10.089, p=0.006 and OR 5.230, 95% CI 1.698-16.106, p=0.004 respectively).

Conclusion:
NH-LGE is associated with exercise load and more prevalent in middle-aged athletes compared to younger athletes and age-matched controls. When present, LGE is not associated with a reduced ventricular function. On the other hand, NH-LGE and reduced RVEF are risk factors for increased ventricular ectopic burden and middle-aged athletes show significantly more complex arrhythmia compared to younger athletes.
Abstract 4145829: Fatty Acid Binding Protein 4 as Potential Indicator for Gestational Diabetes Mellitus-Induced Fetal Endothelial Dysfunction
Authors: Villar Ballesteros Maria de Leyre , Brendel Heike , Hengst Clara , Carstens Philine Sophie , Effenberger Deborah , Mittag Jennifer , Giebe Sindy , Fruehauf Alexander , Birdir Cahit , Taylor Paul , Morawietz Henning
Published: November 2024

Introduction/Background:
Gestational diabetes mellitus (GDM) is the most common complication during pregnancy. GDM is leading to an elevated risk for the development of cardiovascular diseases both in the mother and the child in later life. Previous studies have identified fatty acid-binding protein 4 (FABP4) as a prime candidate involved in the pathophysiology of GDM. Indeed, women with GDM exhibit elevated blood levels of FABP4, suggesting its potential role as a biomarker for endothelial dysfunction and cardiovascular risk assessment in GDM.

Research Question/Hypothesis:
Does FABP4 affect the function of human endothelial cells from patients with GDM?

Goals/Aim:
Our aim is a better understanding of the role of FABP4 in fetal endothelial dysfunction of patients with GDM and the development of potential therapeutic strategies.

Methods/Approach:
Primary human umbilical vein endothelial cells (HUVECs) were isolated from umbilical cords obtained from normoglycemic and GDM pregnancies. Total mRNA from HUVECs was used for bulk RNA sequencing to compare gene expression pattern. HUVECs were subjected to functional analyses assessing proliferation, migration, NO and insulin signaling. Finally, human endothelial cells were exposed to high laminar flow (30 dyn/cm
2
) or simvastatin (10 nM) treatment to investigate their impact on FABP4 expression and endothelial function.

Results/Data:
Bulk RNA sequencing data analysis revealed FABP4 as a gene overexpressed in GDM HUVECs compared to normoglycemic controls. Gene set enrichment analysis showed in addition an enrichment of genes involved in angiogenesis and Notch signaling pathways in human endothelial cells from GDM patients. GDM HUVECs had a significantly higher wound healing capacity compared to normoglycemic controls. The PI3K/AKT/mTOR pathway was enriched in GDM HUVECs. GDM HUVECs displayed impaired activation of AKT and eNOS (expression and phosphorylation) after stimulation with insulin, suggesting a possible insulin resistance. Finally, subjecting HUVECs to high laminar shear stress or simvastatin treatment caused a reduction of FABP4 mRNA expression and an increase of eNOS expression, indicating potential therapeutic strategies to improve endothelial function.

Conclusions:
We provided evidence that FABP4 could be involved in fetal GDM-induced endothelial dysfunction. High laminar shear stress and medications activating eNOS signaling could protect the endothelium against the negative impact of FABP4 in GDM.
Abstract 4145840: Hypertensive Cardiorenal Disease with Cardiorenal Failure vs. Hypertensive Renal Disease with Renal Failure: Racial Mortality Trends from 1999 to 2020 in the United States
Authors: Ashfaq Fatima , Zain Ahmad
Published: November 2024

Introduction:
High levels of blood pressure (BP) are responsible for 7.6 million deaths each year worldwide, more than any other risk factor. The diagnosis of hypertension is associated with a significant increase in the risk of kidney or cardiovascular events, with no prior history of these events. Our study aims to analyze trends in hypertensive heart disease and hypertensive heart and kidney disease-related mortality in the United States, focusing on different races.

Method:
We retrieved death certificate data from the CDC-WONDER database for adults aged ≥25 years. Crude mortality rates (CMRs) and age-adjusted mortality rates (AAMRs) per 100,000 persons were calculated. Temporal trends were examined using the average annual percent change (AAPC) determined by joinpoint regression.

Result:
From 1999 to 2020, a total of 100,705 people died from hypertensive heart and renal disease in the USA. The overall AAMR of 1.4 per 100,000 displayed a trend during this period (AAPC: 4.8, 95% CI [3.3–6.2]). Total deaths from hypertensive heart disease and renal disease associated with heart failure were 5,274, showing an increasing trend from 1999 to 2020. The AAMR for hypertensive heart and renal disease with heart failure was 0.1 (AAPC: 5.2, 95% CI [3.8–6.7]). Black or African Americans have the highest AAMR (0.1, 95% CI [0.1–0.1]). Total deaths from hypertensive heart disease and renal disease associated with renal failure were 34,519, showing an increasing trend from 1999 to 2020. The AAMR for hypertensive heart and renal disease with renal failure was 0.4 (AAPC: 3.9, 95% CI [2.6–5.1]). Black or African American has the highest AAMR (1.6, 95% CI [1.5–1.6]), followed by American Indian or Alaska Native (0.5, 95% CI [0.4–0.5]), Asians and Pacific Islanders (0.4, 95% CI [0.4–0.4]), and White (0.4, 95% CI [0.3–0.4]).

Conclusion:
African Americans and other identified high-risk races should get targeted therapies to reduce the burden of hypertensive-related morbidity and mortality; those with renal impairment should receive special attention. The goals of these interventions ought to be to increase access to healthcare, raise public knowledge of hypertension, and support lifestyle changes.