bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14625: Association of Eicosanoid Metabolites With Cardiac Structure and Function
Authors: Roshandelpoor Athar , Ma Janet , Demirel Ilker , Lau Emily , Alotaibi Mona , Ramirez Fernandez Del Castillo Mariana F , Parekh Juhi , Pan Abigail , Owunna Ndidi , Varadarajan Vinithra , Jain Mohit , Cheng Susan , Lima Joao AC A , Ho Jennifer E
Published: December 2023

Introduction:
Eicosanoids are bioactive lipids that govern the upstream initiation of pro- and anti-inflammatory activity. They may serve as important pathways by which obesity and cardiometabolic disease lead to the development of heart failure with preserved ejection fraction (HFpEF).

Objective:
We sought to examine the association of plasma circulating eicosanoid metabolites with subclinical cardiac remodeling as ascertained by cardiac magnetic resonance imaging (CMR) as important determinants of HFpEF risk.

Methods:
We studied 3880 MESA study participants (mean age 63±10 years, 53% women) who underwent plasma metabolite profiling using a mass spectrometry-based platform and CMR. We used multivariable linear regression to examine the association of eicosanoid metabolites with left ventricular mass index (LVMI, primary outcome), LV end-diastolic volume index (LVEDV), and left atrial volume (LAV).

Results:
Of 811 eicosanoids, 158 were associated with LVMI (Figure; FDR q <0.05 for all). Specifically, derivatives of eicosadienoic acid (15 oxoEDE), linoleic acid (9,10 diHOME), and arachidonic acid (12(R) HETE) were negatively associated with LVMI and prostaglandin 19R-hydroxy-PGE1 was positively associated with LVMI. Of 158 metabolites, 65 were are also associated with LVEDV including derivatives of linoleic acid (13(S) HOTrE), oxylipin 11-HETE and 15 oxoEDE. Of 158 metabolites, Adrenic acid is also associated with LAV.

Conclusions:
We found that specific eicosanoids including 15 oxoEDE, 9,10 diHOME, and 12(R) HETE were associated with LVMI, an important measure of subclinical cardiac remodeling and precursor to HFpEF. As causal drivers of HFpEF are poorly characterized, a better understanding of pro- and anti-inflammatory eicosanoid pathways that contribute to cardiac remodeling may have important implications for the prevention of HFpEF.
Abstract 14640: Community Socioeconomic Distress is Associated With Poor Access to Heart Failure Clinical Trials in the United States
Authors: Chandrabhatla Anirudha S , Horgan Taylor M , Narahari Adishesh K , Yount Kenan W , Teman Nicholas R , Kern John A , Mazimba Sula , BERGIN JAMES D , Yarboro Leora
Published: December 2023

Introduction:
Clinical trials have historically lacked representation from minorities and individuals from lower socioeconomic backgrounds. Little is known about the role geographic access plays in recruiting diverse populations for clinical trials.

Objectives:
Given disparities in clinical trial enrollment, we sought to analyze how access to heart failure trials varies across demographic groups.

Methods:
We queried
clinicaltrials.gov
for trials classified under “heart failure” that are recruiting and enrolling adult patients. Trial site addresses were obtained using Google Maps. We calculated drive times from each US census tract to the closest trial site using ArcGIS Pro v3.1. Demographic information and urban / rural statuses for census tracts were obtained from the US Census Bureau. Distressed Community Index (DCI) scores (0 = no distress, 100 = severe distress) based on metrics including education level, poverty, and unemployment were collected. Data were analyzed using Python v3.8.

Results:
We identified 954 heart failure trials with 644 unique sites in the US. About 54% of the rural population lives more than 30 minutes from a trial site compared to 22% of the urban population (OR 0.23;
p
< 0.001). Analysis of DCI scores covering 328 million people revealed that drive times increase with higher socioeconomic distress (
p
< 0.001; Figure). In both urban and rural settings, median drive times for individuals in the top 10% of distressed communities (56 min urban and 79 rural) are more than three times those of individuals in the lowest 10% of distressed communities (18 min urban and 23 rural). A larger proportion of non-white minorities live less than 30 minutes from a trial site compared to the white population (77% vs. 60%; OR 2.23;
p
< 0.001).

Conclusions:
Increased socioeconomic distress is associated with worse access to heart failure trial sites for both urban and rural populations. Geographic barriers should be addressed to improve diversity in trials.
Abstract 14644: Healthcare Resource Utilization and Economic Burden Due to Atrial Fibrillation in Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy: Real-World Analysis of 2016-2021 Claims Data
Authors: Butzner Michael , Sen Sounok , Stendahl John C , Papademetriou Eros , Potluri Ravi , Liu Xing , Heitner Stephen B , Jacoby Daniel L , Shreay Sanatan , Sohn Regina L , Freeman James V
Published: December 2023

Introduction:
Atrial fibrillation (AF) is common among patients with symptomatic obstructive hypertrophic cardiomyopathy (soHCM), but the impact of AF on healthcare resource use (HCRU) and cost is not well studied.

Hypothesis:
Comorbid AF increases HCRU and cost among patients with soHCM.

Aims:
To assess HCRU and charges (per person per year [PPPY], in USD) for patients with vs without comorbid AF.

Methods:
Symphony medical and pharmacy claims data were assessed from 2016-2021 to identify (by ICD-10 code) adult patients with treatment-naïve soHCM in the United States. We defined symptomatic as fatigue, chest pain, syncope, dyspnea, heart failure, or palpitations within 3 months of index date and comorbid AF as AF within 3 months of index date. Patients entered the cohort once they received their index soHCM pharmacotherapy or soHCM surgery treatment; and were required to be on soHCM pharmacotherapy (beta-blockers, calcium channel blockers, or disopyramide) or to have had a procedure for soHCM (septal reduction therapy, pacemaker, or implantable cardioverter defibrillator).

Results:
Of 9490 patients with soHCM, 2681 (28.3%) had AF. For patients with vs without AF, median age was 68 years vs 63 years (
p
<0.0001), 48.0% vs 42.5% (
p
<0.0001) were male, and mean (SD) Charlson Comorbidity Index was 2.4 (2.0) vs 1.5 (1.8). Patients with vs without AF had ~44% more outpatient (OP) visits (14.75 vs 10.22), more urgent care visits (5.95 vs 4.88), and higher charges ($50,936 vs $32,254) PPPY (Table). Total all-cause charges were ~60% higher for those with vs without AF ($70,902 vs $44,035 PPPY) (Table).

Conclusions:
In this large, US-based cohort of patients with symptomatic oHCM, those with vs without comorbid AF had substantially more OP visits and charges PPPY. Our data show that comorbid AF in patients with soHCM is associated with a significantly greater healthcare resource use and economic burden, emphasizing the need for new treatments to prevent or improve AF.
Abstract 14672: Exercise Hemodynamic Profiles of Resting and Exercise-Based Definitions of Cancer Therapy-Related Cardiac Dysfunction in Anthracycline-Treated Breast Cancer Survivors
Authors: Foulkes Stephen , Howden Erin , Haykowsky Mark J , Antill Yoland , Janssens Kristel , Nightingale Sophie , Wright Leah , Costello Ben , La Gerche Andre
Published: December 2023

Introduction:
Detection of cancer therapy-related cardiac dysfunction (CTRCD) is a cornerstone of heart failure (HF) risk assessment. However, it is unclear how closely CTRCD definitions reflect typical HF features of reduced exercise tolerance (VO
2
peak) and blunted cardiac reserve.

Hypothesis:
Standard CTRCD metrics (resting LVEF and GLS) will show poor agreement with reduced VO
2
peak and changes in cardiac reserve following anthracycline chemotherapy (AC).

Methods:
This analysis used baseline (pre-AC) and 12-month assessments from a randomized trial of exercise training in breast cancer patients (n=104) undergoing AC ± anti-HER2 therapy. Assessments included resting echocardiography (LVEF and GLS), cardiopulmonary exercise testing (VO
2
peak) and exercise cardiac magnetic resonance (peak cardiac output [CO], stroke volume [SV] and LVEF [LVEF
peak
]). CTRCD was defined as ≥10% absolute decline in LVEF to a value <50%, >15% decline in GLS, and a ≥10% decline in VO
2
peak from pre-AC.

Results:
Seventy-nine participants (76%) completed pre-AC and 12-month assessments, 14 of whom (18%) met LVEF and 30 (38%) met GLS CTRCD criteria (10% met both criteria). In addition to declines in resting LVEF and GLS, these participants showed a reduction in LVEF
peak
, but no change in peak SV, CO or VO
2
peak (Figure 1A-B). In contrast, 19 participants (24%) had a ≥10% VO
2
peak decline (-17% vs Pre-AC, P<0.001) that coincided with a decline in peak SV (-6%, P=0.03), and LVEF
peak
(-11%, P=0.02), with no significant change in resting LVEF or GLS (Figure 1C). Of those who met VO
2
peak criteria, only three (16%) and five (26%) met LVEF or GLS criteria, respectively, and only one met all three criteria.

Conclusions:
Whilst capturing reduced global LV systolic function, CTRCD definitions are insensitive to meaningful declines in VO
2
peak and cardiac reserve. Incorporating measures of VO
2
peak into CTRCD surveillance may improve HF risk stratification in breast cancer survivors.
Abstract 14681: Coronary Artery Calcium is Associated With Cardiovascular Disease and Poorer Survival in Patients Undergoing Autologous Hematopoietic Cell Transplantation
Authors: Wu Stephanie Y , Rhee June W , Iukuridze Aleksi , Bosworth Alysia , Chen Sitong , Atencio Liezl , Manubolu Venkat , Bhandari Rusha , Jamal Faizi , Mei Matthew , Herrera Alex , Forman Stephen , Nakamura Ryotaro , Wong Lennie , Budoff Matthew J , Armenian Saro
Published: December 2023

Background:
Hematopoietic cell transplantation (HCT) is an established curative treatment for patients with hematologic malignancies, however survivors are at a >4-fold risk of cardiovascular disease ([CVD] heart failure, myocardial infarction, stroke]) compared to the general population. Coronary artery calcium (CAC) is predictive of CVD in non-oncology patients; less is known about its association with CVD risk and outcomes after HCT.

Methods:
This was a retrospective cohort study of 243 consecutive patients who underwent first autologous HCT for Hodgkin/non-Hodgkin lymphoma between 2009-2014 with no history of CVD. CAC was determined from chest computed tomography performed <60d from HCT; measurements (Agatston unit) were made by trained researchers blinded to patient demographics and outcomes. CAC was categorized as: 0, 1-100, >100. Multivariable Cox regression analysis was used to calculate hazard ratio (HR) estimates and 95% confidence intervals (CI), adjusted for covariates (age, conventional risk factors [e.g. hypertension, dyslipidemia], cancer treatment).

Results:
Median age (range) at HCT was 55.7y (18.5y-75.1y), 59% were male; race/ethnicity: non-Hispanic white (60%), Hispanic (25%), Asian (11%), Black (4%); prevalence of CAC was 37%. The 5y CVD incidence for the cohort was 12%, and there was an incremental increase according to CAC score: 0 (6%), 1-100 (20%), >100 (32%); p=0.001 (Figure 1A). CAC was significantly associated with CVD risk (HR 3.0, 95%CI 1.2-7.5) and worse 5y survival (77% vs. 50% p<0.001 [Figure 1B]; HR 2.0, 95%CI 1.1-3.4), compared to those without CAC.

Conclusions:
CAC is an important and independent predictor of CVD and survival after HCT. Taken together, these data form the basis for integration of readily available imaging information into decision making prior to HCT (e.g. pre-habilitation, non-HCT approaches) or after HCT (e.g. cardiac rehabilitation), setting the stage for strategies to optimize outcomes after HCT.
Abstract 14690: ProduceRX Clinical Trial
Authors: Nau Claudia , Wu Jason H , Han Bing , Habib Mina , Gu Zheng , Li Xia , Chao Ceping , Schwartz Pam , Mozaffarian Dariush
Published: December 2023

Background:
Nutrition related cardiometabolic diseases are leading causes of morbidity, health disparities and health care spending. Produce prescriptions are highly promising to address these issues but impacts on health outcomes have not been tested in a randomized controlled trial.

Hypothesis:
A pre-randomized controlled trial that provides 6 months of free weekly produce deliveries to the intervention group reduces hemoglobin A1c (HbA1c), body mass index (BMI), and blood pressure (BP), among Medicaid patients with type 2 diabetes (T2DM) and persistently elevated HbA1c when compared to the control group.

Methods:
A total of 450 eligible Kaiser Permanente Southern California patients were enrolled 1:1:1 into control, high- and low-dose intervention groups. Eligibility criteria included: being enrolled through Medicaid (MediCal), age 18+ years, having T2DM with at least two HbA1c values > 7.5% in the past 12 months. Produce amounts were scaled to household size and ranged from $90-270 and $90-180 for high and low-dose households, respectively. The primary endpoint was change in HbA1c at 6 months (measured up to 90 days post-intervention). Secondary outcomes were changes in BMI and BP. Primary analysis assessed both intervention groups compared to control; exploratory analyses considered dose-response. Analysis was conducted using random effects models.

Results:
Participants were predominantly Hispanic (85%), female (65%), and in average 59.4(SD=13.2) years old. At baseline, HbA1c was 9.40% (1.52); BMI 34.1kg/m2 (7.95); 74% had elevated BP or hypertension (stage 1 or 2), 58.3% were food insecure. Baseline characteristics were similar between control and intervention groups, 87% of participants had a 6-month HbA1c measure. In intention-to-treat analysis, compared to control, HbA1c at 6 months was significantly reduced in the intervention group: -0.37 [95%CI:-0.71;-0.04],p=0.028. Reduction in HbA1c was not significantly different between the high- and low-dose intervention. Results for BMI and BP are forthcoming.

Conclusion:
In the first randomized controlled trial of its kind, a produce prescription program significantly improved HbA1c among low-income patients on Medicaid with poor glycemic control at baseline.
Abstract 14692: Clonal Hematopoiesis Driver Mutations Have Disparate Effects on Macrophage Cytokine Profiles and Only Modestly Drive Atherogenesis at Pathophysiological Levels
Authors: Carter Paul , Kar Siddhartha , Kitt Lauren , Figg Nichola , Quirós Pedro , Zhou Ang , Burgess Stephen , Vassiliou George , Libby Peter , Bennett Martin , Clarke Murray C
Published: December 2023

Background:
Clonal hematopoiesis (CH) is characterized by expansion of hematopoietic stem cells due to somatic mutations in leukemia-associated genes. CH is associated with increased mortality, attributed to cardiovascular disease (CVD) driven by increased IL-1β from clonal macrophages. However, different CH-driver mutations perturb diverse genes with distinct functions and reports of IL-1β release from mutant macrophages are discordant. Furthermore, directionality of the association between CH and CVD is not established.

Hypothesis:
We hypothesized that mutations of common CH-driver genes have disparate effects on macrophage cytokine profiles and atherogenesis. We also hypothesized that atherosclerosis-driven systemic inflammation promotes clonal expansion.

Methods/Results:
We characterised cytokine expression in LPS-treated murine bone marrow-derived macrophages (BMDMs) harboring CH-driver mutations (
Tet2
,
Dnmt3a
, or
Jak2
). Transcript level of
Il1a
,
Il1b
and
Il6
was increased ~3-5 fold in
Tet2
-/-
and
Dnmt3a
-/-
BMDMs, but only ~1.5-2 fold with heterozygotic loss, which mimics more closely patients with CH. Notably,
Tet2
-/-
BMDMs (but not
Dnmt3a
or
Jak2
) release more IL-1α/β, accompanied by increased Asc specks and caspase-1 activity, implying heightened NLRP3 inflammasome activation.

In murine chimera models of CH,
Tet2
-/-
and
Tet2
+/-
cells (but not
Dnmt3a
or
Jak2
), expand under the steady state. Clonal dynamics were unaffected by systemic inflammation via exogenous IL-1α, or high fat diet-induced atherogenesis in
Ldlr
-/-
recipients.

Atherosclerotic plaques in murine CH models at 12 weeks are only mildly increased with heterozygotic
Tet2, Dnmt3a,
or
Jak2
mutations (10-20%). Observational and Mendelian randomisation analyses of UK BioBank did not reveal bidirectional associations between CH and atherosclerosis.

Conclusions:
We demonstrate augmented NLRP3 inflammasome activation in
Tet2
-/-
BMDMs and disparate effects of different CH mutations on cytokine profiles. We find no evidence for atherosclerosis or systemic inflammation driving clonal expansion. Thus, the pathogenesis of CH-driven disease should be treated as different entities for each mutation and likely involves overlapping or distinct mediators.
Abstract 14718: Systolic-Diastolic Coupling and Cardiac Limitations to Exercise in Patients With Hypertrophic Cardiomyopathy
Authors: Turlington William , Dias Katrin , Hearon Christopher , Ivey Erika , Delgado Vincent , Brazile Tiffany , Turer Aslan T , Link Mark S , Sarma Satyam , Levine Benjamin D , Macnamara James P
Published: December 2023

Background:
Exercise intolerance occurs in patients with hypertrophic cardiomyopathy (HCM) in part due to impaired augmentation of stroke volume (SV reserve) and diastolic dysfunction. Systolic-diastolic (S-D) coupling characterizes how systolic contraction of the left ventricle (LV) primes efficient elastic recoil during diastole. S-D coupling declines with age and is further reduced in patients with heart failure. Impaired S-D coupling may contribute to impaired cardiac response to exercise in patients with HCM.

Hypothesis:
We hypothesized that S-D coupling is associated with peak oxygen uptake (peak VO
2
) and peak cardiac output (Qc) patients with HCM.

Methods:
Patients with HCM (HCM: n=25, age=46 ± 8.9 years) and healthy, sedentary adults (CON: n=115, age=50 ± 9.7 years) underwent cardiopulmonary exercise testing and resting echocardiography. S-D coupling is the relationship between LV longitudinal excursion of the mitral annulus during systole (S
exc
) and early diastole (ED
exc
) measured with tissue Doppler imaging. Peak VO
2
(Douglas bag), peak Qc (C
2
H
2
rebreathe), and SV reserve were assessed during maximal treadmill exercise. Linear regression was performed between S-D coupling and peak VO
2
, peak Qc, and SV reserve and multivariate regression with age as a covariate.

Results:
S-D coupling was reduced in HCM (HCM: 0.56±0.10, CON: 0.63±0.08, p <0.001). In CON, S-D coupling was independently associated with age (r = 0.52, p <0.001), but not peak VO
2
(r = 0.26, p = 0.473) or peak Qc (r = 0.04, p = 0.538). In HCM, S-D coupling was associated with peak VO
2
(r = 0.46 p = 0.019) and peak Qc (r = 0.56, p = 0.003) with a trend in SV reserve (r = 0.36, p = 0.071) (Figure), independent of age (VO
2
p = 0.020, Qc p = 0.004).

Conclusion:
Impaired systolic-diastolic coupling is associated with fitness and the cardiac response to exercise in patients with HCM. Inefficient S-D coupling may link insufficient stroke volume generation, diastolic dysfunction, and exercise intolerance in HCM.
Abstract 14728: Implementation of a Resident-Led Cardiac Point-of-Care Ultrasound Curriculum for the Internal Medicine Residency Program at UT Southwestern
Authors: Gulati Jaskeerat , Yen Christine , Almonte Matthew , Shah Parth , Hoeting Natalie , Godfrey Sarah , Bhatt Anish B
Published: December 2023

Introduction:
The American Society of Echocardiography recommends integration of cardiac point-of-care ultrasound (cPOCUS) into training programs. There is no defined strategy on how to create and implement this on a large scale.

Aim:
To implement and assess the efficacy of a novel, pilot-tested, resident-led, simulation-based cPOCUS curriculum within the Internal Medicine (IM) internship at UT Southwestern (UTSW).

Methods:
All 62 categorical interns in the 2022-2023 class in the UTSW IM residency program completed our cPOCUS curriculum during their outpatient weeks over a three-month period. All tests and workshop guides were developed by current IM residents, cardiology fellows and faculty in a fashion that is reproducible annually, even as residents and fellows change. All interns underwent two educational workshops. Workshop 1 focused on acquisition and recognition of basic cardiac anatomy. Workshop 2 focused on abnormal cardiac pathology. Pre-and post-tests assessed their ability to identify cardiac windows, identify abnormal cardiac pathology, and rate their comfortability on a 5-point Likert scale.

Results:
Analysis was conducted on 39 of 62 responses containing both pre- and post-tests. Of the 39 interns, 6 (15%) scored below 70% on the pre-test. On the post-test, 38 out of 39 (97%) interns scored at least 80%. Furthermore, 4 of the 6 lowest scoring interns on the pre-test scored 100% on the post-test. There was a significant increase in the average pre- and post-test scores by 6% (p=0.02), with greatest improvement in the ability to identify LVEF <40% (12% increase). Post-curriculum, 33 of 39 interns (85%) “agreed” or “strongly agreed” that they felt comfortable interpreting cPOCUS, compared to only 3 of 39 interns prior.

Conclusions:
Our simulation-based cPOCUS curriculum was successfully implemented within a large intern class at an academic center, with a 100% participation rate. Post-curriculum, there was a significant increase in cPOCUS interpretation scores and increased comfort with acquisition and interpretation. Our curriculum is sustainable, requires minimal cost, and serves as an archetype for the implementation of simulation-based cPOCUS curricula into “inpatient month + clinic week” block-based training programs.
Abstract 14746: Association of Left Atrial Late Gadolinium Enhancement With Electrogram Abnormalities, Tissue Impedance, and Proximity to the Aorta
Authors: Khoshknab MirMilad , Zghaib Tarek , Xu Lingyu , Zado Erica , Callans David J , Marchlinski Francis , Han Yuchi , Markman Timothy , Desjardins Benoit , Nazarian Saman
Published: December 2023

Introduction:
Left atrial (LA) late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) predominates near the aorta(AO); however, LGE does not equate fibrosis and may be artifactual or indicate expanded interstituim.

Hypothesis:
We sought to examine the association of LA LGE with proximity to the descending and ascending AO and use regional impedance and voltage measurements to dissect the mechanism of LGE .

Methods:
The retrospective cohort included consecutive patients who underwent pre-procedural CMR and atrial fibrillation (AF) ablation between January 2016 - 2021. The association of voltage amplitude, impedance, and image intensity ratio (IIR) at each electroanatomic map point with distance from the nearest AO point was examined after adjustment for age, sex, AF type, AO stenosis, LA volume, and AO diameter.

Results:
Included 63 patients (age 65.5±8.8 years, 33% female). Among 42 ablation naive patients, distance from AO was unassociated with bipolar and unipolar voltage amplitudes, but associated with impedance (+0.04 ohm/mm, P=0.011) and IIR (-0.03 /mm, P<0.001). Among 21 patients with prior ablation, distance from AO was unassociated with IIR, but associated with bipolar (+0.01 mV/mm, P<0.001) and unipolar (+0.01 mV/mm, P=0.001) voltage amplitudes and impedance (+0.03 ohm/mm, P=0.025).

Conclusions:
Given lower impedance but normal voltage, de novo peri-AO LA-LGE likely signifies expanded interstitium, rather than fibrosis or fat infiltration. Following ablation, peri-AO voltage and impedance are both decreased compared to other LA regions, suggesting that peri-AO lesion delivery is more effective, likely due to lower impedance at baseline.
Abstract 14748: Unheard Voices: The Burden of Ischemia and No Obstructive Coronary Artery Disease in Women
Authors: Maayah Marah , Chowdhury Nazar , Walenczyk Kristie , Mazure Carolyn M , Burg Matthew , Spatz Erica S , Bernabeo Michelle , Ritchie Jessica , Shah Samit
Published: December 2023

Introduction:
Ischemic heart disease (IHD) is a leading cause of morbidity and mortality in women. Up to two-thirds of women with IHD suffer from ischemia with no obstructive CAD (INOCA), which includes endotypes such as microvascular dysfunction and vasospasm. Due to a lack of clear prognostic data, INOCA has historically been viewed as a benign condition, and many women have been dismissed from cardiovascular care despite refractory symptoms and a risk for adverse outcomes.

Hypothesis:
Women with INOCA have a high burden of symptoms and significant functional limitation due to poorly controlled symptoms, which can be characterized with a structured interview.

Methods:
We enrolled 41 women with INOCA who underwent clinically-indicated invasive coronary physiology testing. Structured interviews were performed to elicit symptom characteristics, limitations, and perception of illness. Data extracted from the interviews was analyzed using the constant comparison method to determine common themes among women with INOCA.

Results:
The most common symptoms in our sample included chest pain (n=38, 93%), dyspnea (35, 85%), fatigue (32, 78%), and abnormal heart rhythms (27, 66%). Most patients experienced symptoms daily (24, 59%) and reported that their symptoms were severe (33, 80%). They expressed limitations to instrumental activities of daily living (25, 61%), hobbies (23, 56%), work (19, 46%), and travel (11, 27%). Many reported a sense of foreshortened future (26, 63%), a feeling of invalidation by providers and loved ones (25, 61%), and difficulty getting a diagnosis (31, 76%). After receiving a diagnosis, they reported positive outcomes such as reduced stress and better understanding of disease management (38, 93%).

Conclusions:
Women with INOCA have significant impairment in quality of life due to frequent anginal symptoms. Feelings of invalidation were common, and many patients reported multiple incorrect diagnoses. After receiving a diagnosis, they reported reduced stress, improvement in illness perception, and hope for improved health in the future. These findings demonstrate the importance of recognizing INOCA and incorporating advances such as physiology-guided medical therapy into routine practice.
Abstract 14756: The Effect of Torsemide vs Furosemide Across the Renal Function Spectrum - Insights From the TRANSFORM-HF Trial
Authors: Martens Pieter , Greene Stephen J , Mentz Robert J , Li Shuang , Wojdyla Daniel , Eisenstein Eric , Anstrom Kevin , Pitt Bertram , Velazquez Eric J , Tang Wai Hong W
Published: December 2023

Introduction:
Among patients discharged after hospitalization for heart failure (HF), a strategy of torsemide versus furosemide showed no difference in all-cause mortality or hospitalization.

Hypothesis:
Clinicians may favor torsemide in the setting of renal dysfunction due to better oral bioavailability and longer half-life. However, the impact of baseline renal function on these findings is unknown.

Methods:
The TRANSFORM-HF trial randomized patients hospitalized for HF to a long-term strategy of torsemide versus furosemide, and enrolled patients across the spectrum of renal function excluding patients on dialysis. In this post-hoc analysis, baseline renal function during the index hospitalization was assessed as tertiles of estimated glomerular filtration rate (eGFR) (using 2021 CKD EPI formula), blood urea nitrogen (BUN), and BUN/creatinine ratio. The interaction between baseline renal function and treatment effect of torsemide vs furosemide was assessed for endpoints of (1) all-cause mortality and (2) all-cause mortality and all-cause readmissions at 12 months.

Results:
Of 2859 patients randomized, 336 (11.7%) had eGFR<30ml/min/1.73m
2
, 1138 (39.8%) had eGFR 30-60 ml/min/1.73m
2
, and 1385 (48%) had eGFR≥60ml/min/1.73m
2
. Baseline eGFR and BUN did not clearly modify the treatment effect of torsemide vs furosemide for either all-cause mortality
(Figure, Panel A)
or all-cause mortality and all-cause readmissions at 12 months
(Figure, Panel B)
. For the composite outcome, BUN/creatinine ratio showed evidence of heterogeneity of treatment effect potentially in favor of torsemide in the middle tertile (interaction p-value<0.01).

Conclusion:
Across the spectrum of baseline eGFR and BUN, a strategy of torsemide versus furosemide did not significantly impact mortality or readmission outcomes following hospitalization for HF..
Abstract 14771: Chronotropic Incompetence and Response to Exercise Training by HIV Status in the Exercise for Healthy Aging Study
Authors: Durstenfeld Matthew S , Wilson Melissa P , Jankowski Catherine , Ditzenberger Grace L , Longenecker Chris T , Erlandson Kristine M
Published: December 2023

Background:
People with HIV (PWH) have lower exercise capacity compared to HIV-uninfected peers. Chronotropic incompetence (CI), the inability to increase heart rate during exercise, may contribute to reduced exercise capacity. We hypothesized that PWH would have lower adjusted heart rate reserve (AHRR=(HR
peak
-HR
rest
)/(220-Age-HR
rest
), a measure of chronotropy, normal >80%) and that AHRR would improve with exercise training.

Methods:
The Exercise for Healthy Aging Study included sedentary adults ages 50-75 with (PWH) and without HIV (controls) recruited for a 24-week exercise training program. Participants exercised at moderate intensity for weeks 1-12 and were then randomized to continue moderate or advance to a higher intensity of exercise for weeks 13-24. We compared prevalent CI on treadmill cardiopulmonary exercise testing by HIV. We compared AHRR and change in AHRR from baseline to 12 and 24 weeks by HIV status using mixed effects models. Finally we explored whether improved chronotropy could explain the greater benefit of exercise observed among PWH.

Results:
Among 32 PWH and 37 controls (median age 56, 7% female, mean BMI 28 mg/m
2
), 9/31 (29%) with HIV compared to 4/38 (11%) controls had CI (p=0.07). At entry, AHRR was lower among PWH (91 vs 102%; difference 11%, 95%CI 2.5-19.7; p=0.01). At week 12, AHRR normalized among 27 PWH (+8%, 95%CI 4-11; p<0.001) and sustained at week 24 (+5, 95%CI 1-9; p=0.008) compared to no change among 31 controls (95%CI -4 to 4; p=0.95; p
interaction
=0.004). Accounting for AHRR, the greater benefit of exercise observed among PWH at 12 weeks (peak VO
2
+1.5 ml/kg/min more than controls, 95%CI 0.1 to 2.9, p=0.04) was attenuated (0.4 ml/kg/min independent of AHRR, 95%CI -0.9 to 1.8; p=0.53). After 24 weeks of exercise, only 4/26 (15%) PWH met the definition for CI compared to 3/29 (10%) of controls (p=0.70).

Conclusions:
Chronotropic incompetence may contribute to reduced exercise capacity among PWH and improve with exercise training.
Abstract 14779: Whole Exome Sequencing Study in Pediatric Postural Orthostatic Tachycardia Syndrome Unveils a Path Forward From Genes to Drugs
Authors: Qu Huiqi , Glessner Joseph , Chang Xiao , Mentch Frank , Liu Yichuan , Bakay Marina A , Boris Jeffrey , Hakonarson Hakon
Published: December 2023

Introduction:
Postural orthostatic tachycardia syndrome (POTS) is more common in Caucasian individuals with a positive family history, while the risk in females is ~4-times of that in males. To date, the etiology of POTS is poorly understood.

Hypothesis:
Integrative sequencing and translational approaches to identify its genetic underpinning may better understand its pathogenesis and molecular mechanisms for the development of novel precision-based therapies.

Methods:
We adopted exome sequencing to evaluate the etiology and molecular mechanisms of POTS. We examined a unique collection of 87 unrelated pediatric POTS cases (61 females and 26 males, 6~21 years old), using exome sequencing. Non-relationship between individuals were validated by genome wide genotyping and identity by descent (IBD) analysis.

Results:
All the individuals were classified as European by principal component analysis (Figure 1). We identified 184 pathogenic (P) or likely pathogenic (LP) variants (in 162 genes). Sixty-eight (78%) cases have at least one P/LP variant. Each P/LP mutation is supported by a minimum of two databases, including ClinVar, InterVar or HGMD_Pro_2023.1. Over-representation analysis (ORA) by the DisGeNET approach showed the enriched gene sets of muscle hypotonia and epilepsy/seizures with statistical significance (FDR<E-10). Clinically, among the 87 WES patients, 41 (47%) suffered from chronic fatigue, and 13 (15%) patients have the symptoms of epilepsy, seizure or convulsion. A number of drug targets in these gene sets are highlighted, including vitamin D receptor, carbamoyl-phosphate synthase 1, methylmalonyl-CoA mutase, androgen receptor, and phenylalanine hydroxylase.

Conclusions:
Our results suggests that chronic fatigue and epilepsy/seizure symptoms are comorbid symptoms in POTS patients, resulting from common genetic defects. Future precision-based therapies targeting these specific genetic defects may lead to improved outcome in POTS.
Abstract 148: Differential Neuroprotective Effects of Targeted Temperature Management in Adult and Aged Rats Post-Cardiac Arrest
Authors: Chen Binjie , Su Chenglei , Zhao Ningjun , Xu Tie , Yan Xianliang
Published: December 2023

Background:
Targeted temperature management (TTM) has been recognized as a crucial brain protective method post-cardiac arrest (CA). However, its efficacy has recently been questioned due to several clinical trials.

Hypothesis:
TTM may not offer significant neuroprotective benefits in older individuals post-CA.

Aims:
This study aims to evaluate the therapeutic efficacy of TTM on neurological dysfunction in aged rats post-CA.

Methods:
Fifty-six male Sprague-Dawley (SD) rats were divided into two age groups: adult group (3-4 months, n=28) and aged group (19-22 months, n=28). Each group was then randomized into four subgroups: 1) sham, 2) sham + TTM, 3) control, 4) control + TTM. Control and control + TTM groups underwent 6 minutes of asphyxiation followed by cardiopulmonary resuscitation. TTM was applied at 32-34°C for 2 hour post-return of spontaneous circulation (ROSC). Neurological outcomes were assessed five days post-CA using the Y-maze and the Open field test. Serum IL-17 and IL-6 levels were measured four hours post-CA.

Results:
TTM significantly enhanced the spontaneous alternation in the Y-maze (p <0.05), increased moter active in Open field test (p<0.05), and reduced serum IL-17 and IL-6 levels in the adult group (p <0.05). Conversely, in the aged group, TTM did not exhibit any significant benefits in Y maze performance, Open field test, IL-17 or IL-6 serum levels reduction (p >0.05).

Conclusion(s):
TTM demonstrated improvement in post-CA neurological deficits in adult rats, yet it failed to deliver similar benefits in aged rats. IL-6 and IL-17 might play a role in the differential neuroprotective effects of TTM.
Abstract 14806: Rate of In-Hospital Initiation of SGLT2 Inhibitors Remains Low Despite Reduction in Rate of 30-Day Readmission From Heart Failure Exacerbation
Authors: Saleki Massoud , Hitt Juvena , Van Buren Peter
Published: December 2023

Introduction:
Heart failure (HF) management guidelines recommend starting SGLT-2 inhibitors (SGLT2i) for symptomatic HF to reduce rates of HF hospitalization and cardiovascular mortality. However, in-hospital initiation of SGLT2i for titration has yet to be strongly recommended. In this study, we sought to evaluate the effect of in-hospital initiation of SGLT2i on the rate of 30-day HF-related readmission from an index admission for HF exacerbation at the University of Vermont Medical Center (UVMMC).

Hypothesis:
Patients who are admitted for an HF exacerbation who are discharged on SGLT2i from their index admission are less likely to be readmitted from an HF-related cause within 30 days of discharge compared to patients who are not started on an SGLT2i, though a minority of eligible patients will be started on SGLT2i during this time.

Aims:
The aims of this study are to 1) compare 30-day HF-related readmission rates between patients discharged on SGLT2i during their index admission, and patients not on SGLT2i, and 2) describe the proportion of patients not currently on SGLT2i who appear to be eligible.

Methods:
We conducted a chart review of 122 patients admitted to UVMMC from July to December 2022 with an HF exacerbation. We recorded patient and index admission descriptors, including ejection fraction, other GDMT (BB, RAASi, MRA), comorbidities, demographics, and admission duration. We then determined if 1) an HF-related readmission occurred within 30 days, 2) the patient was an acceptable candidate for SGLT2i, and 3) SGLT2i was present on discharge.

Results:
Among 122 patients admitted with an HF exacerbation at UVMMC, the 30-day HF-related readmission rate of patients discharged on SGLT2i was 3.7%, compared to 8.5% for patients not started on SGLT2i. Of these 122 patients, while 116 (95.1%) were acceptable candidates for SGLT2i, only 27 (23.3%) were discharged on SGLT2i, with 8 more (6.9%) eventually started on SGLT2i.

Conclusions:
Our review affirms guidelines that recommend starting SGLT2i in patients with symptomatic HF to reduce rates of HF hospitalization. Despite these guidelines, adoption rates remain low due to a variety of factors. Improving in-hospital SGLT2i initiation rates would benefit HF patients and the healthcare systems that support them.
Abstract 14818: Endothelial Specific Deletion of
Uchl1
Attenuates the Development of Pulmonary Hypertension
Authors: Chu Aiai , jia yangfan , Luo Ang , Liang Shuxin , Bao Changlei , Tang Haiyang , Desai Ankit A
Published: December 2023

Introduction/Background:
While ubiquitination of proteins plays an important role in the development of pulmonary arterial hypertension (PAH), little is known about the role of deubiquitinases (DUBs) and, more specifically, ubiquitin carboxyl-terminal esterase-L1 (UCHL1), in this process. Our prior work reported that reductions in endothelial UCHL1 lead to increased degradation and reduced activated levels of Akt1. Given the pathologic role of Akt1 in PAH, we now hypothesize that endothelial UCHL1 deficiency leads to reductions in activated Akt1, resulting in the attenuation of PAH.

Methods/Results:
Tissues from animal PH models, as well as human PA endothelial cells (hPAEC) from patients with PAH, exhibited increased vascular staining and protein expression of UCHL1. Inhibition of UCHL1 in cell culture reduced vascular endothelial growth factor (VEGF)-induced angiogenesis, proliferation and migration of hPAECs. Endothelial-specific
Uchl1
knockout mice (
Uchl1
EC-/-
) demonstrated reduced right ventricular hypertrophy (RVH), RV systolic pressures (RVSP), and improved right heart function compared to control mice exposed to chronic hypoxia. Consistent with these findings, histologic examination revealed significantly improved vascular medial thickness and remodeling as well as reduced total and activated Akt1 levels in the lungs of hypoxia-exposed
Uchl1
EC-/-
mice compared to hypoxia-exposed control mice.

Conclusions:
Our findings reveal that a specific deficiency of
Uchl1
in the endothelium results in PAH attenuation via reduced Akt1, highlighting a novel therapeutic target.
Abstract 14822: Portopulmonary Hypertension Unveiled: Effects of Transjugular Intrahepatic Portopulmonary Shunt Placement
Authors: Ekpo Eson J , Ng Daniel , Patel Malhar
Published: December 2023

Introduction:
Transjugular intrahepatic portosystemic shunts (TIPS) treat portal hypertension by connecting the portal vein to the hepatic vein in the liver. The resultant shunting of portal venous flow to the systemic circulation helps reduce the portosystemic gradient and is used to treat complications of portal hypertension. Right heart failure and the development of pulmonary hypertension after TIPS are known complications; however, portopulmonary hypertension (POPH) is rare.

Description of Case:
A 61-year-old male presents to the clinic for six months of exertional dyspnea, weight gain, and lower extremity edema. He has a history of coronary artery disease and nonalcoholic steatohepatitis cirrhosis, with TIPS placement four years prior for esophageal variceal bleeding. An echocardiogram revealed right ventricular (RV) dilatation with moderately reduced function, a flattened left ventricular septum, and an estimated pulmonary artery systolic pressure of 91 mmHg. An echocardiogram and right heart catheterization (RHC) performed before his TIPS showed normal RV function and pulmonary artery pressures (PAP).

Decision Making:
The patient was promptly started on furosemide and spironolactone, and after adequate diuresis, a repeat RHC was obtained, which showed significantly elevated PAP, and normal left-sided filling pressures and cardiac output. Other causes of pulmonary hypertension were ruled out, and the patient was started on tadalafil monotherapy for severe POPH, with significant improvement in his PAP (Table 1).

Conclusion:
POPH after TIPS is a rare complication that should be suspected in patients presenting with signs of right-sided volume overload. The mechanism by which TIPS leads to POPH is not entirely understood. The degree of RV dysfunction correlates with mortality, and prompt treatment is warranted.
Abstract 14826: Effect of Torsemide vs Furosemide After Discharge for Acute Heart Failure Across the Spectrum of Left Ventricular Ejection Fraction: Observations From Transform-HF
Authors: Kapelios Chris J , Greene Stephen J , Mentz Robert J , Ikeaba Uchechukwu , Wojdyla Daniel , Anstrom Kevin J , Eisenstein Eric L , Pitt Bertram , Velazquez Eric J , Fang James C
Published: December 2023

Introduction:
TRANSFORM-HF trial showed no significant difference in mortality or hospitalization outcomes in patients randomized to torsemide (T) versus furosemide (F) following a heart failure (HF) hospitalization (HFH). However, outcomes and responses to some therapies differ across ejection fraction (EF) subgroups.

Methods:
We compared baseline patient characteristics and described treatment effects for various endpoints in TRANSFORM-HF stratified by EF: HF with reduced (EF≤40%;HFrEF) vs mildly reduced (41-49%;HFmrEF) vs preserved (≥50%;HFpEF) EFs. We also evaluated the prognostic association between EF and outcomes. Study endpoints were all-cause mortality and hospitalization at 30 days and 12 months (separately and as composites), and total hospitalizations.

Results:
Our analysis included 2635 patients with EF data. Participants with HFpEF were older (72 [62-79] years) with lower eGFR (52 [36-72] ml/min/1.73m
2
) compared to the other EF cohorts, while patients with HFrEF had lower systolic blood pressure (112 [101-125] mmHg) and higher NT-proBNP levels (4554 [2368-9620] pg/ml). The neutral treatment effect for all studied endpoints did not differ across EF groups (all interaction p-values>0.05, Figure 1A). There was no significant difference in the rates of mortality and/or hospitalization at 12 months between patients in the three EF groups (HFrEF 59.2, HFmrEF 61, HFpEF 63 events/100 patient-years, p=0.24, Figure 1B). Even after adjusting for covariates the relative risk or rate ratio for all endpoints did not differ across EF groups.

Conclusions:
Despite baseline differences between EF cohorts in TRANSFORM-HF, there were no significant differences in the study endpoints with T versus F across the EF spectrum. In contrast to previous observations, the adjusted risk ratios for all study endpoints did not differ by baseline EF. Following a HFH, there is substantial risk for all-cause mortality and subsequent hospitalization independent of EF.
Abstract 14829: Inflammatory Cells and Cytokines Are Increased in Mice With Pulmonary Arterial Hypertension Associated With Hematopoietic Dnmt3a Depletion
Authors: Emon Isaac , Al-Qazazi Ruaa , Lima Patricia , Martin Ashley , Rauh Michael , Archer Stephen L
Published: December 2023

Background:
Pulmonary Arterial Hypertension (PAH) is characterized by pulmonary vascular remodeling of the precapillary pulmonary arteries. Increasing evidence suggests that inflammation plays an essential role in PAH development. Understanding the involvement of immunity in this context can provide valuable insights into the pathogenesis of PAH.
DNA Methyltransferase 3A
(
DNMT3A
) mutations can lead to altered DNA methylation patterns in immune cells, potentially affecting the expression of immune-regulatory genes. Here, we investigate the role of inflammation in PAH driven by hematopoietic Dnmt3a depletion in mice.

Methods:
We used male and female conditional, Vav-Cre-driven hematopoietic
Dnmt3a
knockout mice (
Dnmt3a
–/–
) and compared them to controls (n=3/group). Lung tissue and plasma were collected. Single-cell suspensions of digested lungs were stained to detect total leukocytes (CD45+), T cells (CD3+), B cells (CD19+), macrophages (Ly6G-, F4/80+), and neutrophils (Ly6G+, F4/80-) via flow cytometry. Plasma samples were screened for 32 distinct cytokines using a cytokine array.

Results:
Dnmt3a
–/–
mice spontaneously developed PAH at 4.5 months. PAH was associated with a 19% increase in total CD45+ leukocytes in the lungs compared to controls. T cells, and B cells were increased in
Dnmt3a
–/–
mice compared to controls (7.9% and 3.1%, respectively). In contrast, there was no difference in lung neutrophil count. Two subsets of macrophages were observed based on granularity. Compared to controls,
Dnmt3a
–/–
mice had a 29% increase in agranular macrophages and a 19.7% increase in granular macrophages. IL-13, known for its role in alternative monocyte/macrophage activation in PAH patients associated with systemic sclerosis (SSc-PAH), was significantly increased in the plasma of
Dnmt3a
–/–
mice compared to controls (1.8 times higher, p=0.02). IL-12p40, a chemoattractant for macrophages, showed a trend towards being increased in
Dnmt3a
–/–
mice compared to controls (5.7 times higher, p=0.14).

Conclusion:
Deletion of
DNMT3A
in the hemopoietic system triggers an inflammatory form of PAH in mice, associated with increased macrophages, B- and T-cells in the lung. IL-13 may be a potential diagnostic marker in PAH.
Abstract 14833: Association of RV Hemodynamics From 4D Flow CMR With RV Restrictive Physiology From Pediatric to Adult Repaired Tetralogy of Fallot
Authors: ZHAO XIAODAN , Tan Ru-San , Hu Liwei , Chai Ping , Bryant Jennifer A , Teo Lynette Li San , Fortier Marielle V , Yeo Tee Joo , Leng Shuang , Ouyang Rongzhen , Allen John , Hughes Marina , Garg Pankaj , van der Geest Rob , Yip James , Tan Teng Hong , Tan Ju-Le , Zhong Yumin , Zhong Liang
Published: December 2023

Introduction:
Right ventricular restrictive physiology (RVRP) is common after repair of Tetralogy of Fallot (rTOF), especially with residual pulmonary regurgitation. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) quantitates biventricular blood flow components and kinetic energy (KE) parameters, but their association with RVRP is unclear. We aimed to study 4D flow CMR parameters in adult and pediatric rTOF patients vs healthy controls and associations of 4D flow parameters with RVRP in rTOF.

Methods:
103 rTOF patients (40 pediatric, 63 adult; age 24±17 years; 53M:50F) and 171 healthy controls (14 pediatric, 157 adult; age 40±15 years; 97M:74F) were prospectively recruited from centers in Singapore (2) and China (1) to undergo 4D flow CMR on multi-vendor scanners. LV and RV flow components—direct flow, retained inflow, delayed ejection flow and residual volume—and KE parameters (normalized to end-diastolic volume, KEi
EDV
)—global, peak systolic, average systolic, average diastolic, peak E-wave and peak A-wave—were analyzed. KE discordance was calculated as the ratio of RV and LV average systolic KEi
EDV
.

Results:
See Table. RVRP was identified in 70 patients (68%). rTOF with RVRP exhibited higher median RV stroke volume index, RV ejection fraction, RV direct flow, RV peak E-wave and E-wave/A-wave, and lower RV residual volume compared to rTOF without RVRP (all P<0.05). Using binary multivariable logistic regression analysis—and after adjustment for age, pulmonary regurtitation, LV and RV ejection fraction, RV direct flow was found to be independently associated with RVRP in rTOF (P<0.001).

Conclusion:
Patients with RVRP had higher RV direct flow, RVEF and RV peak E-wave energy, indicating the potential compensatory adaptations in patients with RVRP.