bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15187: Risk Factors for Type B Dissection in Marfan Syndrome: The Cornell Aortic Aneurysm Registry
Authors: Narula Nupoor , Devereux Richard B , Arbustini Eloisa , Ma Xiaoyue , Weinsaft Jonathan W , Girardi Leonard N , Malonga Grace P , Roman Mary J
Published: December 2023

Introduction/Background:
With improvements in the medical and surgical management of patients with Marfan syndrome (MFS), type A dissections are decreasing. As a corollary, most MFS dissections are now type B, for which risk factors remain largely uncertain.

Research Questions/Hypothesis:
In this prospective and retrospective observational study, we explore determinants of type B dissection risk in a large single-center MFS registry through analysis of systematic clinical and imaging data over four decades.

Goals/Aim:
Determinants of type B dissection risk in MFS will inform appropriate prognostication, management, and treatment of this patient population.

Methods/Approach:
Demographic and anthropometric features, cardiovascular disease, and surgical history were compared in MFS patients with and without type B dissection.

Results/Data:
Of 335 MFS patients, 56 (17%) experienced a type B dissection (versus type A in 9%). Patients with type B dissection were more likely to have undergone elective aortic root replacement (ARR; 75 vs. 46%, p<0.001). 55% of patients had type B dissection a mean of 14.1 years after ARR, whereas 45% experienced type B dissection before ARR. Valve replacement was more common than valve-sparing repair in those with post-operative type B dissection (27% vs. 12%, p=0.02), although this difference was eliminated after adjusting for duration of post-operative follow up. 50 (89%) patients were aware of their MFS diagnosis prior to type B dissection. Among those with pre-dissection imaging, the descending aorta was normal or minimally dilated in 87%. In multivariable analyses, patients with type B dissection were more likely to have undergone ARR, mitral valve surgery, had a type II dissection, and to have lived longer.

Conclusions:
In our contemporary cohort, type B dissections are more common than type A. The associations of type B dissection with ARR, mitral surgery, and type II dissection suggest a more severe phenotype in the setting of prolonged life expectancy.
Abstract 15197: Differential Impact of Factor XII, Factor XI and Prekallikrein Deficiency on Thrombosis: A Pro-Thrombotic Vascular Action of Bradykinin
Authors: Hu Lejia , Xu Pengfei , Wang Miao
Published: December 2023

Objective:
Factor XII (FXII) initiates the plasma contact system that triggers the intrinsic coagulation pathway and the kallikrein-kinin pathway via factor XI (FXI) and plasma prekallikrein (PK), respectively. The importance of the contact system for thrombosis sparing hemostasis is well established, however a comprehensive head-to-head comparison of the three proteases in arterial thrombosis is missing.

Approach and Results:
We produced mice deficient in FXII (

F12
-/-

), FXI (

F11
-/-

) and PK (

Klkb1
-/-

) and compared them in two distinct thrombosis models. While all (100%) of WT mice formed occlusive thrombi upon 30% ferric chloride challenge, carotid artery occlusion was reduced to 0, 4.8, 27.3 % in

F12
-/-

,

F11
-/-

and

Klkb1
-/-

mice (n=14-22), respectively. Upon photochemical-induced cremaster arteriolar thrombosis, occlusion time (s) prolonged to 226.1±60.4, 123.8±32.0 and 87.8±25.3 (mean±SEM, n=10-15) respectively in

F12
-/-

,

F11
-/-

and

Klkb1
-/-

mice, largely exceeding WT levels (38.3±12.1). A discordance was observed between
in vivo
thrombotic effects of the proteases and their roles for
ex vivo
coagulation, which ranked FXII≈FXI>PK as assayed by thromboelastography and activated partial thromboplastin time. Activation of FXII promoted thrombosis in WT and

Klkb1
-/-

mice, and impressively, it also accelerated thrombosis in

F11
-/-

mice, increasing activated PK activity and plasma bradykinin formation. Infusion of bradykinin and blockade of degradation of endogenous bradykinin increased platelet-endothelium adhesion and promoted thrombotic occlusions, which involved bradykinin mediated endothelial cell-release of platelet activating factor, rather than direct activation of platelets by bradykinin.

Conclusion:
FXII, FXI and PK differentially mediate experimental thrombosis
in vivo
and FXII/FXI appear as superior targets for thrombosis as compared to PK. PK- bradykinin axis activated by FXII contributes to thrombosis
in vivo
.
Abstract 15225: Hybrid Coronary Revascularization versus Percutaneous Coronary Intervention for True Left Main Bifurcation Lesions
Authors: Yang Cheng , Sui Yong-Gang , Wu Yong-Jian
Published: December 2023

Introduction:
Hybrid coronary revascularization (HCR) is an alternative and feasible treatment for true left main bifurcation lesion.

Aims:
This study sought to compare the clinical outcomes of patients with true left main bifurcation lesions undergoing revascularization by HCR or percutaneous coronary intervention (PCI).

Methods:
This was a propensity-matched cohort study. From March 1, 2010, to March 31, 2018, 40 consecutive patients with true left main bifurcation lesions underwent HCR at Fuwai Hospital. These patients were matched 1:1 to 40 contemporaneous patients who underwent PCI. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of cardiac mortality, myocardial infarction, stroke, and repeat revascularization.

Results:
There were no differences in patient characteristics between the two groups. During a mean follow-up of 2 years, MACCE occurred in 12 patients (3 in the HCR group and 9 in the PCI group). Kaplan-Meier survival analyses indicated that the cumulative incidence of MACCE (log-rank test,
p
= 0.026) and repeat revascularization (
p
= 0.011) in the HCR group were significantly lower than those in the PCI group.

Conclusions:
Compared with PCI, HCR demonstrated satisfactory mid-term outcomes in MACCE for true left main bifurcation lesions.
Abstract 15234: Greater Statin Interruption Rates and Lower Adherence for Women versus Men With HIV in the United States
Authors: Davy-Mendez Thibaut , Kinlaw Alan C , Okeke Nwora , Floris-Moore Michelle , Eron Joseph J , Berry Stephen A , Crane Heidi M , Golin Carol E , Napravnik Sonia , Simpson Ross J
Published: December 2023

Introduction:
People with HIV, particularly women, have an elevated CVD risk, and a recent trial showed they can benefit from statin initiation even at low/moderate predicted CVD risk. Yet <50% of patients with HIV on statins experience adequate lipid reductions. To inform efforts to reduce CVD risk and gender disparities in this population, we examined statin persistence and adherence by gender in a nationwide sample of privately insured people with HIV.

Methods:
Among people with HIV ≥18 in MarketScan Commercial Claims who initiated a statin in 2015-2020, we used outpatient pharmacy claims to estimate 1) time to statin interruption (first gap >30 days) and 2) monthly proportion of days covered (PDC) by a statin. PDC analyses censored people if they were off statins ≥6 months. We estimated gender differences in interruption rates using hazard ratios (HR) and in having low adherence (PDC<80%) using risk ratios (RR) adjusted for age, calendar year, US census region, and employment status.

Results:
There were 7809 statin initiators (17% women; 60% in the South; median age 52 years, IQR 47-57). Two years after statin initiation, 81.0% (95% CI 78.1%-83.8%) of women and 69.8% (68.4%-71.3%) of men had ≥1 statin interruption (adjusted HR women vs. men 1.35 [1.25-1.46]) (Fig. 1A). Monthly PDC decreased in the first 6 months of statin use to 61% for women and 68% for men, then increased to 73% and 80%, respectively, after 2 years (Fig. 1B). Over all months, women more commonly had PDC<80%, with an adjusted RR of 1.27 (1.20-1.34).

Conclusions:
People with HIV had high statin interruption rates and adherence <80% at most time points, with disparities for women versus men. It is possible that, despite having insurance, women with HIV in this sample are more affected than men with HIV by socioeconomic and other barriers to statin adherence. Gender-specific efforts in people with HIV should address these barriers to promote adherence to CVD preventative pharmacotherapy in this population at high risk.
Abstract 15253: Phenotyping Sub-Populations of Heart Failure Patients Based on Clinical and Social Determinants of Health Using Unsupervised Machine Learning Models
Authors: Spinelli Kateri J , Li Hsin Fang , Rider deanna , Abraham Jacob , Spatz Erica S , Huang Xiaoyan
Published: December 2023

Background:
Social determinants of health affect health care utilization, access, and outcomes. When designing population health management strategies, phenotyping sub-populations of patients using both clinical and social risk factors is essential.

Aims:
Define sub-populations of heart failure (HF) patients using a novel machine learning method based on demographics, comorbidities, and social vulnerability. Compare days alive and out of hospital (DAOH) within 1-year post-discharge.

Methods:
Retrospective cohort study of patients admitted to 48 hospitals in Providence St. Joseph Health with a primary HF diagnosis from 02/01/2016 - 12/31/2022. CDC social vulnerability index (SVI) was linked to patients’ home address. Thirty-four demographic, clinical, and SVI variables were included in the model. Clusters were defined using hierarchical clustering of principal components (HCPC). Top drivers of cluster formation were assessed by v-test . Due to large sample size, 10 random samples were selected and clusters were assigned by vote. Cluster enriched subgroups (CES) were defined as patients having ≥6 cluster assignments and >80% cluster vote.

Results:
HCPC analysis grouped 61,126 hospitalizations into 3 clusters (Figure). CES-1 patients (n=25,873) were older, wealthier, White, with multiple comorbidities living in more educated communities. CES-2 patients (n=13,450) were younger with combined systolic/diastolic HF and fewer comorbidities living in crowded, urban communities. CES-3 patients (n=3,787) were non-White, Hispanic with higher cardiometabolic risk factors living in urban, crowded, low-income communities. CES-1 patients had fewer DAOH (230) and higher 1-year (22%) mortality. CES-2 patients had similar DAOH (274) to CES-3 (269), despite younger age and fewer comorbidities.

Conclusions:
In a large heart failure cohort, unique sub-populations based on clinical and social factors have distinct care needs, utilization, and outcomes.
Abstract 15303: The SGLT2 Inhibitor Canagliflozin Attenuates Fibrosis and Mitochondrial Dysfunction Induced by Hyperglycemia in Isolated Primary Human Cardiac Fibroblasts
Authors: Varzideh Fahimeh , Jankauskas Stanislovas , Kansakar Urna , Lombardi Angela , Santulli Gaetano
Published: December 2023

Background:
Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been recently approved as antidiabetic drugs showing beneficial effects on major adverse cardiac events. The exact mechanisms underlying the favorable cardiac actions are mostly unknown.

Methods:
Human cardiac fibroblasts (HCFs) were cultured in 5mM glucose (normal glucose; NG), 30mM glucose (high glucose; HG) or 30mM with 1μM SGLT2is empagliflozin (EMPA), dapagliflozin (DAPA), canagliflozin (CANA), and ertugliflozin (ERTU)-containing medium for 24h. RNA-sequencing, Western blots, proliferation rate, Ca
2+
imaging, mitochondrial reactive oxygen species (ROS) were performed on HCFs.

Results:
HG induced a greater mitochondrial ROS production compared to NG, which was attenuated by SGLT2is. Specifically, we observed less ROS in the CANA group in comparison to EMPA, DAPA, and ERTU. In addition, sodium-hydrogen exchanger-1 (NHE-1) was upregulated in HG and such upregulation was markedly mitigated by SGLT2is, particularly by the CANA. Therefore, we continued other experiments using CANA. RNA-sequencing data revealed a clear segregation between HG and HG plus CANA. Strikingly, we observed upregulation of some genes (including
NEAT1
,
RNY1
related to cardiac fibrosis) in the HG group, which were downregulated in HG plus CANA. CANA significantly reduced proliferation rate compared to NG and HG. Compared to NG, HG significantly increased expression of Collagen I, Smad-2, mitochondrial fission (DRP-1) protein, and Beclin 1 (autophagy marker) which were instead reduced with CANA. Moreover, CANA upregulated mitochondrial fusion (MFN-1) protein. We assessed the difference in Ca
2+
flux in HCFs: HG decreased the capacity of the endoplasmic reticulum (ER) to accumulate Ca
2+
and delayed storage-operated Ca
2+
entry (SOCE); treatment with CANA partially prevented loss of ER Ca
2+
storage capacity and significantly improved SOCE timing.

Conclusion:
Our data indicate that CANA attenuates fibrosis, autophagy and mitochondrial dysfunction in HCFs in HG conditions and that this effect might be mediated through NHE-1 inhibition.
Abstract 15304: Nature Exposure and Cardiovascular Outcomes in a Large Metropolitan Area: The Role of Access to Nature
Authors: Makram Omar M , Nwana Nwabunie , Pan Alan P , Nicolas Charlie , Gullapelli Rakesh , Javed Zulqarnain , Maddock Jay E , Kash Bita , Nasir Khurram
Published: December 2023

Background:
Previous studies have found conflicting results regarding the association between greenspaces and cardiovascular health. We aimed to investigate the relationship between cardiovascular risk factors (CVRF) and diseases (CVD), and NatureScore, as well as access to nature using the Walk Score.

Methods:
Cross-sectional study including one million adult patients in Houston Methodist Outpatient Registry (2016-2022) living in the greater Houston metroplex. NatureScore is a composite score of natural environment exposure and quality of greenspace calculated for each patient. NatureScore was categorized as follows: nature-deficient/light (0-39), nature-adequate (40-59), nature-rich (60-79), and nature-utopia (80-100). Walk Score was divided into 4 categories: car-dependent (all errands) (0-19), car-dependent (most errands) (20-39), somewhat walkable (40-59), and very walkable/ walker’s paradise (60-100).

Results:
A total of 1.07 million patients (mean age 52, female 59%, Hispanic 16%, NHB 14%) were included with median NatureScore of 69 and 99% living in urban areas. The prevalence of CVRF and CVD (CAD, PAD, and stroke) was significantly higher in patients living in neighborhoods with high NatureScore without taking access to nature into account (Figure). On adjusting for access to nature (Walk Score), patients living in the highest NatureScore areas had 9% lower odds of any CVRF and 4% of any CVD, than those living in the lowest NatureScore areas. On stratification by Walk Score, those living in high NatureScore high walkability areas had lower odds of CVRF than those in high NatureScore low walkability areas (Figure).

Conclusion:
Our findings suggest that greenspace can positively impact cardiovascular health, yet its accessibility plays a crucial role in determining its actual effect. Our results can guide stakeholders in allocating resources for population health improvement and urban design that consider both exposure and access to nature.
Abstract 15340: Octacosanol Exerts Anti-Inflammatory Effects on Primary Human Aorta Endothelial Cells (HAEC) Induced With Lipopolysaccharides (LPS)
Authors: Tang Jingrong , Lucero Diego , Li Wenling , Liu Huaitian , Kun Julia , Sviridov Denis , Yang Zhi-Hong , Mukoyama Yosuke , Remaley Alan T
Published: December 2023

Atherosclerosis is a complex process characterized by chronic systemic inflammation, endothelial dysfunction, retention of lipoproteins, plaque formation in large and medium-sized arteries, and has become one of the most common causes of death in the elderly nowadays. Octacosanol, a very long chain (C28) aliphatic alcohol, is believed to be the main active ingredient in the Policosanol, which is extracted from plants, such as sugar cane and wheat germ. Policosanol has been used as a potential diet supplementary to improve fatigue, obesity and lipid metabolism. Previous animal studies have shown that both Policosanol and Octacosanol can significantly ameliorate formation of atherosclerotic lesion. To further explore the possible mechanism of Octacosanol on the formation of atherosclerosis, we examined the anti-inflammatory effects of Octacosanol on HAEC treated with LPS at 100ng/ml FBS-free cell culture medium. LPS treatment significantly enhanced human monocyte (THP1) adherence to HAEC cells in time-dependent and dose-dependent style, but Octacosanol at 1.25 or 2.5 μM markedly blocked the adhesion of THP1 to HAEC. ELISA showed that LPS can significantly increase the expression of inflammatory cytokines and adhesion molecules by HAEC at 100ng/ml within 4 hours. LPS stimulated more than 3-fold of release of IL-6, IL-8, MCP-1 at 4 hours. By flow cytometry and ELISA, LPS dramatically increase the expression of PE-Selectin and VCAM-1. When HAEC were pretreated with Octacosanol (1.25μM or 2.5μM), it significantly reduced the release of inflammatory cytokines, MCP-1(p<0.01), IL-6 (p<0.001) and IL-8(P<0.001), and inhibited the expression of PE-selectin(p<0.001) and VCAM-1(P<0.001). Confocal imaging analysis of HAEC cells showed Octacosanol considerably reduced the expression of PE-Selectin and VCAM-1 and VE-Cadherin, leading to the maintenance of cell membrane integrity and underlying ECM and the prevention of THP1 cell adherence. By RNAseq analysis, Octacosanol inhibits LPS-induced inflammatory pathways related to NFKB
2
and RAS-related signaling. In summary, the beneficial effects of octacosanol on atherosclerosis appears to be related, at least partially to, is potent anti-inflammatory effects in cytokine-induced cell adherence.
Abstract 15350: Differing Impacts of Cardiac Implantable Electronic Device Leads on Tricuspid Regurgitation
Authors: Leon Sophie A , Austin Melissa A , Parikh Chitra , Ahmad Danial , Tchantchaleishvili Vakhtang , Pavri Behzad B
Published: December 2023

Introduction:
Placement of cardiac implantable electronic devices (CIED) is thought to contribute to tricuspid regurgitation (TR). However, there are relatively few data comparing the impact of different CIED lead types on the incidence and progression of TR.

Aims:
This study sought to quantify the change in TR severity following implantation of CIEDs with different types of leads.

Methods:
Demographic, diagnostic, and outcome data were collected on patients from a single implanter of cardioverter defibrillators (ICD), right ventricle-paced pacemakers (RV-PM), or His bundle-paced pacemakers (His-PM) from 2016 to 2019. Patients with previous CIEDs undergoing upgrade procedures were excluded. Severity of TR was compared before and after CIED implantation using one-sided Wilcoxon-signed rank test.

Results:
A total of 97 patients receiving CIEDs were analyzed, including 23 with ICDs, 63 with RV-PMs, and 11 with His-PMs. Median patient age was 72 years [IQR: 63, 81], and 44% of patients were female. Echocardiograms were obtained a median of 20 days [4, 91] before CIED implantation and 31 months [18, 43] following implantation. Baseline TR grade was comparable between groups (p = 0.65). TR severity significantly worsened after ICD implantation (p = 0.035), RV-PM implantation trended toward worsening TR severity (p = 0.099), and no difference was noted after His-PM implantation (p = 0.68) (Figure). There was no significant change in RA pressure, RV size or function, or LVEF following CIED implantation.

Conclusions:
The effect of CIED leads on TR represents a spectrum related to the type of lead and whether the tricuspid valve is traversed. ICD leads, which are bulkiest and traverse the valve, significantly worsened TR. His-PM leads, which do not traverse the valve, have no apparent effect on TR. The impact of RV-PM leads on TR severity appears in-between ICD and His-PM leads - although the lead traverses the valve, it is lighter than ICD leads.
Abstract 15357: Assessing the Utility of Serial Fetal Echocardiography in Detecting In-Utero Changes for Single Ventricle Lesions
Authors: Ro Sanghee S , Saini Ashish , Morrow Gemma , Ketchum Diana , Kreeger Joe , Michelfelder Erik
Published: December 2023

Introduction:
Current guidelines recommend serial fetal echocardiograms (FE) for fetuses with single ventricle lesions (SV) to identify in-utero changes that can impact delivery management, but there is sparse data on the utility of serial FE. We aim to evaluate the incidence of serial FE changes in fetuses with SV.

Hypothesis:
There is a low incidence of in-utero changes in serial FE for fetuses with SV.

Methods:
Fetuses with SV and > 1 serial visit between 1/1/2012 to 1/1/2023 were retrospectively reviewed. FE were reviewed for significant, defined serial changes in the following: atrioventricular valve, ventricular function, atrial communication, ductus arteriosus, umbilical artery, umbilical vein, systemic venous Dopplers, hydrops, arrhythmias. Fisher’s exact test was used to compare proportions with change between both segmental findings and SV sub-type.

Results:
A total of 721 FE for 248 patients were reviewed, the majority with hypoplastic left heart syndrome (HLHS) (64%) and tricuspid atresia (15%). There was a mean of 2.9 visits per patient and 21 days between FE. Out of 3,699 possible changes, there was a total of 56 (1.5%) changes in 41 patients seen on all follow-up FE (Table 1). The most common changes were worsening atrial level restriction (10, 2.4%) and arrhythmias (10, 2.4%), all of which were premature atrial contractions (p<0.01). Out of 56 changes, only 20 (36%) were critical with clinical impact on perinatal management and 2 (4%) showed progressive, serial worsening. Most changes (85%) were noted in the third trimester. There were no differences in incidence of change on serial FE between SV sub-types (p=0.10).

Conclusions:
SV fetuses have a low incidence of significant physiologic change on serial FE, and progressive worsening of physiologic findings is even rarer. Special consideration should be given to those with HLHS who may develop atrial level restriction. This data should be considered in planning clinical follow-up intervals for fetal SV.
Abstract 15399: Cardiac Sympathetic Nerve Activity in Women With a History of Takotsubo Syndrome: A Novel Stress Myocardial Radionuclide Imaging Strategy
Authors: Chang Joseph T , Mehta Puja K , Nelson Michael D , Maughan Jenna , Lauzon Marie , Hayes Sean W , Friedman John D , Berman Daniel S , Bairey Merz C Noel , Wei Janet
Published: December 2023

Introduction:
Takotsubo syndrome (TTS) is characterized by transient left ventricular (LV) systolic dysfunction, triggered by physical or emotional stress, and associated with increased long-term cardiovascular morbidity. Cardiac iodine-123-meta-iodobenzylguanidine (mIBG) imaging has previously demonstrated sympathetic hyperactivity in the TTS subacute state which improves at follow-up during rest imaging. Cardiac neuronal dysfunction in response to stress has not been evaluated in recovered TTS.

Hypothesis:
Sympathetic hyperactivity, as measured by stress mIBG, is abnormal in TTS after recovery of LV ejection fraction (LVEF).

Methods:
To elicit a sympathetic challenge, women with history of TTS with recovered LVEF (n=19) and asymptomatic age- and sex-matched reference controls (n=10) underwent treadmill (6 minutes) with simultaneous mental-stress testing (public speaking with anger recall). mIBG (10 mCi) was injected during exercise, and planar and SPECT imaging were performed at 15 min (early) and 240 min (late), followed by Tc-99m tetrofosmin myocardial perfusion imaging. Early and late heart-to-mediastinal ratio (HMR) and washout rate (WR) corrected for background were calculated.

Results:
Median time from last TTS event was 23 months (range 4-56). Overall mean age was 60± 12 years, body mass index 25 ± 4kg/m
2
, resting LVEF 70 ± 7%, 41% hypertension and 0% diabetes with no difference between TTS and controls. TTS had higher resting (140 ± 22 vs 123 ± 19 mmHg, p=0.049) and peak (187 ± 17 vs 171 ± 15 mmHg, p= 0.018) systolic blood pressure. While the early HMR and WR were similar, the late HMR was significantly lower in the TTS group (Figure).

Conclusions:
Women with a history of TTS have lower late HMR but similar WR, suggesting neuronal dysfunction in response to sympathetic challenge persists long after recovery from TTS event. Further analysis of catecholamine levels and central nervous system neural pathways will explore the mechanism of dysregulation.
Abstract 15410: Obstacles to Implementation in a Heart Failure Nurse Practitioner and Pharmacist Lead Guideline Directed Medical Therapy Program
Authors: Ali Omaima , Baksh Gladys , Haydo Michele , Reesor Heather , Contreras Carlos , Ahmed Samaa , Kunselman Allen R , Foy Andrew
Published: December 2023

Background:
The aim of this study was to describe differences in baseline characteristics of patients who did or did not complete a HF-GDMT optimization program at our institution and who reached vs did not reach target doses of therapies.

Methods:
We instituted a structured program in September 2020 led by a heart failure nurse practitioner and clinical pharmacist to optimize GDMT in a safe and expedited manner that involved telephone visits and labs every 2 weeks. Since this is an exploratory analysis differences between groups were reported with p values <0.10.

Results:
A total of 247 patients were enrolled. The average age of the cohort was 62.3 (13.9), 31% were women, 53% had new onset within 6 months of enrollment, and 66% were nonischemic. Overall, 198 (80%) patients completed the program and 49 (20%) did not. Non-completers were more likely to have transportation limitations (25% vs 5%;
p<0.001
), to be on Medicare or Medicaid (76% vs 54%;
p=0.009
), to be referred to a prescription assistance program (33% vs 21%;
p=0.084
), and were less likely to have commercial insurance (18% vs 39%;
p=0.008
). Among patients who completed the program only 48 (24.3%) reached the recommended doses of all medicines and 150 (75.7%) did not. Patients who reached the recommended doses were younger (mean age 57.5 vs 64.4;
p=
0.002), and were more likely to have nonischemic vs ischemic cardiomyopathy (29% vs 16%; p=0.078) and chronic vs new onset disease (31% vs 18%; p=0.046). Patients under 50 were far more likely to reach target doses compared to those >80 (46% vs 4%).

Conclusions:
Important differences in patients who did or did not complete the program and who reached or did not reach target doses were identified. These differences help identify implementation challenges in real-world settings.
Abstract 15469: Projected Heart Failure Incidence in US Adults From 2018-2050
Authors: Hennessy Susan , Penko Joanne , Coxson Pamela , Boylan Ross , Bellows Brandon K , Moran Andrew E , Zhang Yiyi , Bibbins-Domingo Kirsten , Beatty Alexis , Kazi Dhruv S
Published: December 2023

Background
Heart failure (HF) currently affects 6.7 million people in the US accounting for $40 billion in annual healthcare costs. Projecting future trends in the clinical burden of HF may guide strategic investments in prevention and treatment as well as workforce planning. This study projects the incidence of heart failure in the US population through 2050.

Methods:
The Cardiovascular Disease (CVD) Policy Model is an established computer-simulation, state-transition model for the US population ages 35-94 years. Age- and sex- specific HF incidence rates were derived from NHLBI pooled cohort studies; the probability of HF hospitalizations associated with coronary heart disease (CHD) or stroke were derived from the National Inpatient Sample and published literature. We applied age- and sex-specific risk factor distributions, incidence, and event rates from 2018 to population projections through 2050 from the US Census. The model estimated absolute number of incident HF cases in subpopulations with CHD (ischemic HF) and without CHD (non-ischemic HF).

Results:
In 2018, 11% of the US population without HF was aged >=75 years, which compares with 16% projected in 2050. The estimated HF incidence rate was higher in males. The annual incidence of HF in US adults aged 35 to 94 years is projected to increase by 39% from 836,000 in 2018 to 1.2 million by 2050 (Table 1). Most incident HF is estimated to occur in the population without CHD, accounting for three quarters of HF in women and over half in men. Among those with HF, the proportion of the population aged >=75 years was projected to increase from 42% in 2018 to 54% in 2050.

Conclusion
A large increase in incident HF is expected in coming years, primarily due to an aging population. Most incident HF is estimated to be non-ischemic. Primary prevention, specifically controlling risk factors associated with non-ischemic HF, may offer the greatest opportunity to reduce HF incidence.
Abstract 15485: Nationally Representative Trends of Overall Physical Activity and Its Subtypes Among US Adults With Diabetes, Hypertension, and Dyslipidemia: Findings From NHANES 2007-2020
Authors: Nabi Wafa , Aminorroaya Arya , Dhingra Lovedeep S , Khera Rohan
Published: December 2023

Background:
Physical activity is associated with reduced risk of CV events. Evaluating the nature of physical activity is essential to target improving CV outcomes.

Methods:
We identified US adults from NHANES 2007-2020 with CV risk factors of DM, hypertension, and dyslipidemia based on self-report, medication history, and lab values. We examined self-reported physical activity, disaggregated into vocational, recreational, and transportational physical activity. We defined adequate physical activity according to AHA guidelines and assessed trends using weighted logistic regression models and complex survey methods.

Results:
Based on 40,336 adult participants of NHANES during 2007-2020 who reported their physical activity, an estimated 68% (95% CI: 67-69) of US adults adhered to the physical activity recommendations in 2017-2020 compared with 62% (60-64) of those with hypertension, 57% (53-61) of those with DM, and 66% (63-69) of those with dyslipidemia. From 2007-2020, overall physical activity significantly increased among US adults and those with hypertension and DM, but not among those with dyslipidemia. Among those at risk for CVD, vocational, recreational, and transportational physical activity accounted for 51-54%, 35-38%, and 10-13% of overall physical activity, respectively, in 2017-2020 (Fig).

Conclusions:
While those with CV risk factors had lower physical activity, with a third of them not adhering to physical activity recommendations, overall physical activity improved during 2007-2020. Vocational physical activity accounts for half of the overall physical activity among those at risk for CVD.
Abstract 15491: Have Heart Transplant Allocation Policy Changes Brought Improvements in Mortality for Children and Adults With Congenital Heart Disease? A UNOS Database Analysis
Authors: Edelson Jonathan B , zhang Xuemei , Ampah Steve , Mavroudis Constantine D , Maeda Katsuhide , Edwards Jonathan J , Lin Kimberly Y , Rossano Joseph , Wittlieb-Weber Carol , O'Connor Matthew
Published: December 2023

Introduction:
The United Network of Organ Sharing (UNOS) made changes to the priority for allocation of hearts for transplantation (HT) in 2016 for pediatric patients and 2018 for adult patients. There are limited data describing the association of these changes with waitlist outcomes in patients with congenital heart disease (CHD).

Methods:
The United Network for Organ Sharing (UNOS) database was queried for pediatric (<18 y/o, PCHD), and adult (18yo-50yo, ACHD), patients with a CHD diagnosis listed for HT. Cohorts were grouped into pre and post-allocation change eras: PCHD 1/1/11-3/21/15 and 1/1/17-12/31/21, ACHD 1/1/15-10/17/18 and 1/1/19 to 12/31/21. Differences in era for survival from the time of listing for HT were compared using competing risk models.

Results:
We identified 3,646 patients listed for HT during the study period including 1,520 PCHD and 432 ACHD pre-allocation change and 1,443 and 251 post. More PCHD patients in the post cohort were supported with ventricular assist devices (7.6% vs 3.2%) while fewer were on inotropes (41% vs 47%), intubated (18% vs 21%) or on ECMO (5.3% vs 7.9%) (p for all <0.01
).
For ACHD, ECMO (4.8% vs 1.9%) and intra-aortic balloon pump (6.8% vs 1.9%) use was more prevalent in the post era (p<0.05 for both). In a competing risk model adjusting for illness severity, the HR for death or waitlist removal within 1 year of HT listing was higher in the pre-allocation era compared to post for PCHD (HR 1.27 [95% CI 1.06-1.52]) but unchanged for ACHD (HR 1.36 [95% CI 0.77-2.41]).
Figure 1

Conclusions:
ACHD patients did not have the mortality benefit from policy changes which other groups, including PCHD, have experienced. Incorporating measures into the allocation system which more completely capture the illness severity that comes with ACHD are warranted, as are strategies to improve long term survival in this growing population.
Abstract 155: The Relationship Between Positive Psychology Factors and Quality of Life in Long-Term Cardiac Arrest Survivors
Authors: Burns Courtney J , Newman Mary M , Vranceau Ana-Maria , Perman Sarah M , Presciutti Alex
Published: December 2023

Introduction:
There is a need to identify factors that can improve quality of life (QoL) post-CA. Long-term CA survivors (i.e., > 1 year) have recommended utilizing positive psychology factors (i.e., psychological strengths that foster well-being) such as mindfulness, existential well-being, and resilient coping to manage survivorship challenges. We explored associations between these factors and QoL.

Hypothesis:
Higher levels of mindfulness, existential well-being, and resilient coping will be individually associated with better physical, psychological, and social QoL.

Goal:
Identify factors associated with improved QoL, that may become intervention targets.

Methods:
Secondary analysis of survey data of long-term CA survivors from the Sudden Cardiac Arrest Foundation. We examined demographic covariates (sex, months since arrest, age, income), self-reported daily memory problems, functional dependence (Lawton Independent Activities of Daily Living Scale), emotional distress (PTSD Checklist-5, Patient Health Questionnaire-4), and positive psychology factors (mindfulness [Cognitive and Affective Mindfulness Scale-Revised], existential well-being [Meaning in Life Questionnaire Presence of Meaning subscale], and resilient coping [Brief Resilient Coping Scale]). We used the WHOQOL-BREF to measure psychological, physical, and social QoL. We conducted 9 multiple regression models to test the individual relationship between each positive psychology factor and each QoL domain, adjusted for demographic covariates, functional dependence, daily memory problems, and emotional distress.

Results:
We included 129 long-term CA survivors (mean age: 52 years, 52% male, 98% white). In adjusted models, higher mindfulness and resilient coping were associated with better QoL in all domains (βs: 0.19 - 0.56, p < 0.03, R
2
= 0.35 - 0.74); existential well-being was associated with better psychological and social QoL (βs: 0.27- 0.36, p = 0.001, R
2
= 0.4 - 0.72).

Conclusion(s):
Greater levels of positive psychology factors were associated with better QoL, even after accounting for emotional, cognitive, and functional sequelae. Future interventions should consider teaching these positive psychology factors to CA survivors.
Abstract 15512: Disrupting the NelfA Dependent RNA pol II Paused Complex in Heart Precipitates Dilated Cardiomyopathy
Authors: Alikunju Saleena , Yang Zhi , Sayed Danish H
Published: December 2023

RNA polymerase II (pol II) pausing, a wide-spread genomic phenomenon regulates pol II dependent transcription and plays a critical role in gene expression during development and disease. Negative elongation factor (Nelf) complex consisting of five subunits, namely NelfA, NelfB, NelfC/D and NelfE, in coordination with Drb sensitive inducing factor (DISF) complex has been implicated in mediating pol II pausing. Structural studies show NelfA is indispensable for nucleation of paused complex. We have reported widespread promoter NelfA occupancy on cardiac genome, and showed that it is required for compensatory gene expression in hearts during cardiac hypertrophy. Here, we examine paused complex, with respect to its interactome, influence on gene expression and cardiac function. Immunoprecipitation of chromatin bound NelfA, followed by mass spectrometry in sham and TAC induced hypertrophied hearts identified Nelf proteins, pol II and Supt5, along with novel partners like Trim28 (chromatin remodeler), Adprhl1 (cardiac restricted, nuclear enriched, involved in DNA repair) and Numa1 (nuclear structural protein). Conditional NelfA knockout mice developed progressive dilated cardiomyopathy (LVID’d: 4.72 ±0.1, LVID;s: 3.96±0.13, %EF: 33.7±2.12, %FS: 16.15±1.12, LV vol;d: 104.5±21.9, LV vol;s: 70.26±5.5) compared to Wt-Cre (LVID’d: 4.16 ±0.09, LVID;s: 3.14±0.12, %EF: 49.1±2.3, %FS: 24.6±1.3, LV vol;d: 77.5±13.9, LV vol;s: 40.9±3.9), with sudden death by 3mths of age, in males and females KO mice compared to Wt-Cre. Interestingly, absence of NelfA resulted in decrease in cardiomyocyte size and increase in apoptosis. Single nuclei RNAseq on these hearts show decrease in cardiac-enriched sarcomeric genes, along with increase in genes involved in fibrosis and endothelial dysfunction. Further, ChIP-seq showed reduced Trim28 and NelfE promoter occupancy on essential gene, while below threshold or absent on cardiac-enriched and selected inducible promoters suggesting disruption of paused complex. Thus, we conclude that NelfA induced paused complex plays an essential role in efficient pol II dependent gene transcription and expression in heart, and deconstruction of the paused complex precipitates cardiac dysfunction and dilated cardiomyopathy
Abstract 15527: Cardiac Magnetic Imaging-Derived First-Pass Perfusion Parameter: New Marker for Cardiac Involvement and Prognosis in Light-Chain Amyloidosis
Authors: Bi Keying , Wan Ke , Xu Yuanwei , Wang JIE , Li Weihao , Chen Yucheng
Published: December 2023

Introduction:
The clinical value of cardiac magnetic resonance (CMR) imaging-derived first-pass perfusion parameters in patients with light-chain (AL) amyloidosis remains unknown.

Methods:
This prospective study included 226 patients with biopsy-proven AL amyloidosis who underwent CMR between November 2011 to June 2021, with 43 healthy volunteers as normal controls. pulmonary transit time (PTT), Corrected PTT (PTTc), and pulmonary transit beats (PTB) were quantified and calculated from first-pass perfusion image. All-cause mortality was defined as the primary endpoint. Receiver operating characteristic curve, Kaplan-Meier analysis and Cox regression were used for statistical analyses.

Results:
PTT [area under the curve (AUC) 0.84], p<0.001, PTTc (AUC 0.84, p<0.001), and PTB (AUC 0.81, p<0.001) were sensitive to identified cardiac involvement in patients with AL amyloidosis. Amongst 226 patients [143 men, 58.80 years ± 9.86], all-cause death occurred in 166 patients (73.5%) during a median follow-up of 35 months (interquartile range, 25-51 months). In multivariable-adjusted cox regression analysis, PTT was an independent predictor of mortality after adjustment for known clinical [HR 1.061, 95% confidence interval (CI) 1.021-1.102, p=0.003], biochemical (HR 1.055, 95% CI 1.014-1.097, p<0.008), and CMR (HR 1.077, 95% CI 1.034-1.123, p=0.002) risk factors, respectively. In the Kaplan-Meier analysis, PTT cutoff value provided further risk stratification in the subgroup of NYHA class III (p=0.039), Mayo stage 2004 III (p<0.001), and transmural late gadolinium enhancement (LGE) pattern (p<0.001).

Conclusions:
CMR Imaging-derived First-Pass Perfusion Parameters were sensitive for the diagnosis of cardiac amyloidosis and aid for further risk stratification in patients with advanced cardiac amyloidosis.
Abstract 15534: Identification of Narciclasine, a Potential Drug to Treat PAH by Unbiased Pharmaco-Transcriptomic Study
Authors: ABI SLEIMAN ANTONELLA , Reem EL-Kabbout , SALEM MABROUKA , Breuils Bonnet Sandra , Martineau Sandra , Bourgeois Alice , Theberge Charlie , Romanet Charlotte , Lemay Sarah-Eve S , Grobs Yann , Boucherat Olivier , Bonnet Sebastien , Provencher Steeve , Potus Francois
Published: December 2023

Introduction:
Pulmonary arterial hypertension (PAH) is a life-threatening vascular disorder characterized by persistent vasoconstriction and detrimental remodeling of the pulmonary blood vessels. This incurable disease is marked by a complex gene expression reprogramming that triggers, among other, metabolic disorders, heightened by inflammation, and the development of a pro-survival phenotype in pulmonary arterial smooth muscle cells (PASMC).We conducted an unbiased transcriptomic study using lung samples from 16 PAH patients and 12 non-PAH controls and identified 4013 differentially expressed genes. Leveraging in silico pharmaco-transcriptomic analysis (utilizing the Lincs and Sigcom databases), we identified narciclasine as a potential drug.

Hypothesis:

Consequently, we hypothesized that narciclasine could offer improvements in PAH.

Methods and Results:
In vivo
, we administered narciclasine treatment (1 mg/kg, 2 weeks, gavage) in a murine model of PH (monocrotaline model, 60 mg/kg, sc.) and observed improved PH hemodynamics (RVSP, PAAT, TPR), reduced inflammation (CD68 immunofluorescence (IF)), decreased PASMC survival (PCNA and cleaved caspase 3 IF), and alleviated adverse vascular remodeling (Elastic van Gieson Stain Kit).
In vitro
, narciclasine exhibited a dose-dependent reduction of cell proliferation (IF: ki67; Western blot Survivin, PCNA and PLK1) and increased apoptosis PAH-PASMC (IF: cleaved caspase 3; Wb: Bax and Bcl2). Transcriptomic study (conducted in treated PASMCs) reveals that the therapeutic effects of narciclasine in PAH may be attributed to decreased glycosylation (Gene Ontology analysis). We further observed increased glycosylation in remodeled arteries from PAH lungs, PH preclinical models, and cultured PASMC (Periodic Acid Schiff Kit). Subsequently, we validated that narciclasine reduced glycosylation and downregulated the expression of glycosylation enzymes (by wb: GFAT, NGT, OGT) both in vitro and in vivo. Statistical tests used: unpaired t (2 groups), ANOVA (> 2 groups).

Conclusions:
In conclusion, our unbiased pharmaco-transcriptomic study identifies narciclasine as a potential therapeutic drug for PAH. Notably, its efficacy appears to be mediated by the reduction of glycosylation.
Abstract 15542: Social Determinants of Health Screening of Patients With Congestive Heart Failure Within Multiple Urban Ambulatory Clinics
Authors: Shah Aaisha , Kapcin Kyle , Puttur Anushree , Tieliwaerdi Xiarepati , Naser Abdallah , Dhital Yadhu , Amoateng Richard , Gadani Mrudula
Published: December 2023

Introduction:
There is a growing body of literature dedicated to understanding the implications of social determinants of health (SDOH) on cardiovascular disease. This study evaluated a pilot of standardized SDOH screening questionnaires in two large urban ambulatory clinics within a quaternary integrated health network in the Northeastern United States.
Goals/Aims:
This study aims to investigate common social determinants of health which may influence patients with congestive heart failure (CHF).

Methods:
A retrospective review of the incidence of SDOH in adult patients from two Internal Medicine outpatient residency clinics between 2020 and 2023 was performed. SDOH assessment was performed at every visit. Multivariate logistic regression analysis was performed to assess the association of SDOH in patients with and without CHF.

Results:
A total of 14,516 patients were evaluated during this study period (mean age 66 years, 62% female). When matched for age and sex, 808 patients with CHF were compared to those without CHF. In matched data, those with CHF were significantly less likely to endorse food insecurity (64.2% vs 94.6%, p<0.05), lack of safety (1.4% vs 2.8%, p<0.05), lack of social connection (34.4% vs 86.8%, p<0.05), and stress (29.1% vs 84.3%, p<0.05). Patients with CHF were more likely (91% vs 26%, p<0.05) to report a positive PHQ-9 depression screen [Table 1]. Patients with CHF were also noted to have a higher incidence of comorbid illnesses.

Conclusions:
Utilization of evidence-based SDOH screening questions in the workflow can help identify key barriers to cardiovascular diseases such as CHF. Multidisciplinary care in patients with CHF may contribute to improved SDOH reporting. Future studies should use qualitative and quantitative data in combination to further evaluate and address barriers to care in patients with CHF.
Abstract 15552: Augmentation of Right Ventricular Strain Dynamics During Direct Mechanical Ventricular Actuation
Authors: Schmitt Benjamin A , Zhou Yirong , Anstadt Mark P
Published: December 2023

Introduction:
Available forms of mechanical circulatory support are associated with significant complications related to blood contact. Direct cardiac compression (DCC) devices avoid blood contact but may impair diastolic function. This derogatory effect of DCC devices may be related to a negative impact on RV function. Direct mechanical ventricular actuation (DMVA) uniquely augments LV diastolic function. The purpose of this study was to evaluate DMVA’s effect on RV function.

Methods:
Ischemic heart failure (HF) was induced using 5 mins of ventricular fibrillation (VF) circulatory arrest in large mature canines (n=9). Hearts were defibrillated and DMVA applied for 15 mins. VF circulatory arrest was subsequently re-induced for 5 mins to generate progressive HF. The experimental protocol was continued for 3 hrs. Intracardiac echocardiography was used to quantify longitudinal strain and peak strain rates in the RV and LV using speckle-tracking algorithms. Two-way ANOVA with Tukey HSD tests were used to evaluate statistical differences in strain metrics (baseline vs. HF vs. DMVA support and LV vs. RV).

Results:
DMVA increased RV fractional area change (DMVA: 0.282 ± 0.011, Mean ± SEM) relative to either baseline (0.221 ± 0.15, p=0.004) or HF (0.170 ± 0.006, p<0.001). DMVA statistically significantly augmented all RV strain metrics relative to either baseline or HF (Table). Additionally, all DMVA strain metrics were statistically significantly greater in the RV than the LV (LV strain: 18.8 ± 0.5 %, p<0.001, LV strain rate: systolic, -1.46 ± 0.04 1/s, p<0.001, diastolic, 1.51 ± 0.04 1/s, p<0.001).

Conclusions:
DMVA substantially improved RV strain dynamics compared to baseline or HF in this model. During DMVA support, strain dynamics in the RV were amplified more than the LV. This RV augmentation is important to achieving balanced biventricular DMVA support. Enhanced diastolic RV and LV augmentation during DMVA remains highly unique when compared to any other devices.