bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10252: Differences in the Transcriptomic Profile of Visceral Fat in Persons With Metabolically “Healthy” versus Metabolically “Unhealthy” Obesity
Authors: Meddeb Mariam , Wolf Risa , Wallace Amelia S , Chu Xin , Florido Roberta , Echouffo Tcheugui Justin B , Matsushita Kuni , Kass David A , Gerstenblith Gary , Kim Sangwon , Ahima Rexford , Wood G , Coresh Josef , Benotti Peter , Wong G William , Ndumele Chiadi E
Published: June 2023

Introduction:
There is varied metabolic dysfunction among persons with obesity. We assessed differences in visceral adipose tissue transcriptome between persons with metabolically healthy and metabolically unhealthy obesity.

Methods:
We studied 40 patients with obesity (mean age 46; median body mass index 46 kg/m
2
) undergoing bariatric surgery at Geisinger Medical Center. Three obesity groups were defined. Two (metabolically unhealthy) had metabolic syndrome (MetS) with diabetes (DM) (MUOD; n=16) or without DM (MUO; n=8). The third (metabolically healthy) had no MetS or DM (MHO, n=16). Omental adipose tissue obtained at bariatric surgery was snap frozen. Total RNA was extracted and RNA sequencing performed using an Illumina platform. Differential gene expression between the 3 groups was analyzed using DESeq2 software and pathway enrichment analysis performed using Gene Ontology.

Results:
Using an adjusted P-value <0.05, 134 genes were upregulated and 114 genes downregulated in patients with MUOD versus MHO. Genes with the highest amplitude of transcriptional differences included lipopolysaccharide binding protein with log2 fold change (l2fc) of 2.2 and Padj= 1.6 10
-7
, osteopontin (l2fc= 1.9, Padj=1.6 10
-7
), chitinase 3 L1 (l2fc= 2.4 Padj= 1.7 10
-4
), carbonic anhydrase 3 (l2fc= -2.6 Padj= 4.8 10
-8
) and perilipin 5 (l2fc= -1.2 Padj= 0.003). GO upregulated pathways were enriched for pro-inflammatory pathways including leukocyte migration, responses to lipopolysaccharide and interleukin-1, and T cell activation (Padj= 1.7 10
-13
, 9.89 10
-11
, 4.9 10
-09
, 1.1 10
-08
respectively). Downregulated pathways were enriched in organic acid catabolic process, fatty acid oxidation and oxidative phosphorylation (Padj= 7.7 10
-20
, 8.6 10
-20
, 1.5 10
-09
respectively). An inflammatory signature was also present in MUO compared to MHO, whereas oxidative processes were not downregulated in those with MUO relative to MHO.

Conclusion:
In patients with class III obesity, we found a heterogeneous visceral adipose tissue transcriptome. A pro-inflammatory signature in visceral fat was found across the metabolic syndrome spectrum. A metabolic signature with decreased oxidative phosphorylation was linked to metabolic syndrome with concomitant diabetes.
Abstract 10257: Diagnostic Yield of Screening and Associated Factors for Transthyretin Cardiac Amyloidosis in Severe Aortic Stenosis
Authors: Abadie Bryan , Hajj Ali Adel , Martyn Trejeeve M , Carmona Rubio Andres , Puri Rishi , Krishnaswamy Amar , Yun James J , Reed Grant W , Hanna Mazen A , Kapadia Samir R , Jaber Wael A
Published: June 2023

Introduction:
Transthyretin cardiac amyloidosis (ATTR-CA) has been associated with severe aortic stenosis (AS), with some studies finding up to 20% of patients who undergo transcatheter aortic replacement (TAVR) have ATTR-CA. New therapies for ATTR-CA have brought significant interest in identifying patients at high risk for this disease. The purpose of this study was to prospectively evaluate the yield of universal testing for ATTR-CA in older patients with severe AS.

Methods:
All patients ≥ 70 years with severe, native, and degenerative AS seen in valve clinic for evaluation of TAVR were referred for technetium-99m pyrophosphate cardiac scintigraphy (PYP scan). Diagnosis was made via a combination of planar grade, heart to contralateral lung ratio, and single positron emission computed tomography/computed tomography. Patients with a positive PYP scan were referred for appropriate laboratory testing to rule out AL amyloidosis. Clinical and echocardiographic factors were correlated with the PYP result.

Results:
Over a 12-month period, 787 patients with severe AS were screened of which 543 met the inclusion criteria. Of these patients, 298 underwent a PYP scan with 232 not undergoing the scan for logistical and scheduling issues during the pandemic. The positivity rate was 4.3% (13/298). Patients with a positive PYP scan had higher rates of carpal tunnel syndrome (54% vs 14%, p <0.001), abnormal global longitudinal strain (> -18%) (100% vs 69%, p=0.044), low stroke volume index (≤35 ml/m
2
) (92% vs 42%, p<0.001), thick intraventricular septum ≥ 1.1 cm (100% vs 79%, p=0.07), and abnormal left ventricular mass index (83% vs 46%, p=0.010).

Conclusions:
The prevalence of ATTR-CA in severe AS is lower than cited in previous studies, likely due to the expanded indication for TAVR. A multiparametric diagnostic algorithm or risk score for ATTR-CA in AS could enhance the yield of screening, reduce cost and unnecessary radiation, and result in more rapid treatment of amyloidosis.
Abstract 10281: Meta-Analysis of Nitroglycerin’s Efficacy in Preventing the Incidence of Radial Artery Spasm and Occlusion During Trans-Radial Catheterization
Authors: Abdelazeem Basel , Abuelazm Mohamed T , Swed Sarya , Gamal Mohamed , Atef Mostafa , Ashraf Mohamad , Noori Muhammad Atif Masood , Lutz Anthony , Santos Volgman Annabelle S
Published: June 2023

Introduction.
Trans-radial artery (TRA) becomes the most common entry route for cardiac catheterization. However, it may cause radial artery spasm (RAS) and subsequent radial artery occlusion (RAO). We conducted a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy of different administration routes of nitroglycerin in reducing RAS and RAO compared to placebo in adult patients undergoing TRA cardiac catheterization.

Methods.
We searched Google Scholar, Web of Science, SCOPUS, EMBASE, PubMed (MEDLINE), and CENTRAL for RCTs up to April 23, 2022. The outcomes of interest were the incidence of RAS or RAO. Pooled risk ratio (RR) with the corresponding 95% confidence interval (CI) in a fixed-effects model was generated using RevMan Software (Version 5.4). We evaluated heterogeneity using I-square and Chi-square tests.

Results.
Eleven trials with 5,814 patients were included. Compared to placebo, the overall results showed that nitroglycerin was effective in preventing RAS (RR: 0.71 with 95% CI [0.59, 0.84], p= 0.0001), and RAO (RR: 0.74 with 95% CI [0.58, 0.94], p= 0.02). However, subgroup analysis according to the route of administration showed statistically significant result with subcutaneous nitroglycerin in prevention both RAS (RR: 0.57 with 95% CI [0.43, 0.77], p= 0.0003) and RAO (RR: 0.39 with 95% CI [0.16, 0.98, p= 0.05) but not intra-arterial nitroglycerine for RAS ((RR: 0.8 with 95% CI [0.63, 1.02], p= 0.07) and RAO (RR: 0.78 with 95% CI [0.6, 1.01], p= 0.06)), neither topical nitroglycerine for RAS ((RR: 0.73 with 95% CI [0.42, 1.24], p= 0.24).

Conclusion.
Our meta-analysis showed that subcutaneous nitroglycerin administration for TRA catheterization may prevent RAS and subsequent RAO compared to placebo. In contrast, intra-atrial and topical nitroglycerin have non-significant outcomes.

Figure 1: Forest plot of the primary outcomes sub-grouped by route of administration (A- RAS, B- RAO). I2: I-squared; CI: confidence interval.
Abstract 10283: Socioeconomic Disparities in Overall and Morbidity Free Survival of Infants With Single Ventricle Heart Disease
Authors: Nunez Gallegos Flora , Tjoeng Yuen Lie , Iqbal Mehren , Lehmann Gloria , Saynina Olga , Chan Titus , Algaze Claudia
Published: June 2023

Prior studies have demonstrated higher odds of mortality for non-white and lower socioeconomic status patients with single ventricle (SV) heart disease. However, these studies have not examined survival through staged surgical palliation or rates of morbidity in this patient population.

We hypothesized that non-white race/ethnicity and lower socioeconomic status were associated with lower overall survival and increased morbidity through 1
st
birthday in patients undergoing SV palliation.

Patients with SV heart disease, live birth, and planned SV palliation in the National Pediatric Cardiology Quality Improvement Collaborative between January 1, 2016, and December 31, 2020, were included. Race/ethnicity, payer, and neighborhood characteristics were analyzed. Morbidity was defined as acute neurological events, unplanned procedures, renal support, cardiac arrest, extracorporeal life support, necrotizing enterocolitis, or surgical site infection. Morbidity-free survival was defined as survival through each stage of palliation without experiencing one of the above morbidities. Cox proportional hazards and multivariable regression modeling were performed to evaluate the association between socioeconomic variables, race/ethnicity, and overall morbidity-free survival to 1st birthday.

There were 2,184 live births with an overall survival to 1st birthday of 76%. There was no difference in survival to 1st birthday between non-Hispanic White, non-Hispanic Black, and Hispanic patients. Patients with government insurance had decreased survival prior to their 1st birthday (HR 0.79, 95% CI 0.64, 0.98 vs commercial insurance). Infants with government insurance had lower morbidity-free survival during stage 1 (OR 0.72, 95% CI 0.59, 0.87) and stage 2 (OR 0.67, 95% CI 0.52, 0.85) hospitalizations. Patients with “Other” race/ethnicity had lower odds of morbidity-free survival to one year of age (OR 0.68 95% CI 0.47, 0.98). Household income and deprivation index were not associated with survival or morbidity.

Infants with government insurance experienced decreased survival to 1st birthday, and those of “Other” race/ethnicity had lower morbidity-free survival. Addressing disparities in these patient populations is an area of ongoing need.
Abstract 10284: Alcohol Consumption and Cardiovascular Outcomes in Patients With Atrial Fibrillation; a RE-LY AF Registry Analysis
Authors: Oraii Alireza , Kirabo Faith , Balasubramanian Kumar , Benz Alexander P , Wong Jorge A , McIntyre William F , Conen David , Healey Jeff S
Published: June 2023

Introduction:
The role of alcohol intake in patients with atrial fibrillation (AF) has been long debated. We aim to assess the association between different alcohol intake levels and cardiovascular outcomes in patients with AF.

Methods:
We performed a cross-sectional analysis of the RE-LY AF registry, which included 15,400 AF patients who visited emergency departments across 46 countries and were followed for one year after the baseline visit. Alcohol intake level was retrospectively ascertained and categorized into abstainers, light (<7 standard drinks [SD]/week), moderate (7-13 SD/week), and heavy drinkers (≥14 SD/week) based on self-reported intake levels. The outcomes of interest were stroke/systemic embolism, heart failure (HF) hospitalization, all-cause mortality, and major bleeding events. Logistic mixed-effects regression models adjusted for baseline covariates were used to calculate the adjusted odds ratios (aOR) and 95% confidence intervals (CI).

Results:
A total of 14,058 AF patients (mean age: 65.9 years; 48% women) with available data on alcohol intake level were included. The odds of stroke/systemic embolism were not significantly increased in light (aOR 0.87, 95% CI: 0.60-1.26), moderate (aOR 0.92, 95% CI: 0.54-1.58), nor heavy drinkers (aOR 0.76, 95% CI: 0.39-1.49) compared to abstainers. Light and moderate drinking, compared to alcohol abstinence, were associated with reduced odds of HF hospitalization (light: aOR 0.75, 95% CI: 0.59-0.95; moderate: aOR 0.57, 95% CI: 0.38-0.85) and all-cause mortality (light: aOR 0.42, 95% CI: 0.30-0.58; moderate: aOR 0.42, 95% CI: 0.26-0.68; heavy: aOR 0.58, 95% CI: 0.35-0.97). Alcohol consumption was not associated with an excess risk of major bleeding events.

Conclusion:
As compared to non-drinkers, light and moderate alcohol drinking in patients with AF are associated with a lower risk of mortality and HF hospitalization, with no difference in thromboembolic and bleeding risk.
Abstract 10292: Factor V Leiden Associated Venous Thromboembolism Risk Declines With Age in the UK Biobank
Authors: Clapham Katharine , Gilliland Thomas , Haidermota Sara , Koyama Satoshi , Natarajan Pradeep
Published: June 2023

Introduction:
Venous thromboembolism (VTE) is a significant cause of morbidity and mortality. The Factor V Leiden (FVL) variant is a well-described genetic risk factor for VTE. The extent to which FVL exerts influence on VTE risk by age is not well understood.

Hypothesis:
The VTE risk conferred by the FVL variant is dependent on age.

Methods:
We utilized a Cox proportional hazards model to calculate the hazard ratio (HR) for incident VTE in individuals in the UK Biobank with one or two alleles of the common FVL variant, rs6025 (chr1:169549811 (GRCh38.p13) C>T) adjusting for age, sex, diabetes mellitus type 2, smoking history, scaled body-mass index, and the first ten principal components. We further examined the relationship of rs6025-related VTE risk with age by performing Cox proportional hazard regression in individuals aged 40-49, 50-59, and 60-69 years. Analyses were conducted in R-4.0.

Results:
Among 413,722 individuals followed for median of 7 years, 3218 (0.78%) incident VTE events occurred. The presence of the rs6025 variant (allele frequency 0.047) was associated with a 1.7 hazard ratio (HR) of VTE (CI 1.38-2.07, p=2x10
-7
) overall. However, the relative effects varied by age with hazard ratios for individuals 40-49 years, 50-59 years, and 60-69 years being 2.34 (CI 1.39-3.93, p=0.0014), 1.76 (1.20-2.58, p=0.0035), and 1.5 (CI 1.18-2.01, p=0.0016) (
Figure
).

Conclusions:
The risk for VTE conferred by the FVL variant appears to decline with age. This finding may help to better identify individuals who would most benefit from FVL screening.
Abstract 10298: Suboptimal Utilization of Validated Diagnostic Predictive Tools and D-Dimer in the Evaluation for Pulmonary Embolism in a New York City Public Hospital
Authors: Kharawala Amrin , Seo Jiyoung , Hernandez Romero Gabriel , Demirhan Yunus Emre , Hache-Marliere Manuel , Tavares Santos Heitor , Barzallo Diego , Vegivinti Charan Thej Reddy , Balasubramanian Prasanth , Duarte Gustavo J , Alhuarrat Majd Al Deen , Karamanis Dimitrios , Nagraj Sanjana , Varrias Dimitrios , Palaiodimos Leonidas
Published: June 2023

Introduction:
Computed tomography with pulmonary angiography (CTPA) is the gold standard for diagnosis of pulmonary embolism (PE). A nearly five-fold increase in the use of CTPA was observed from 2004 to 2016 in the United States.

Hypothesis:
Suboptimal utilization of validated diagnostic predictive tools with D-dimer might have led to excessive use of CTPA in a large public hospital in Bronx, New York.

Methods:
We conducted a retrospective review of patients who underwent CTPA from January to October 2021. Two independent reviewers, blinded to each other and to the CTPA and D-dimer results, estimated the clinical probability for PE using the Well’s criteria, YEARS criteria, and the revised Geneva score. Patients were classified based on the presence or absence of PE in the CTPA. Chi-square and Fischer's exact test were used to compare discrete variables.

Results:
504 patients were included in the analysis (median age: 56 years, female: 59.1%). The clinical probability for PE was considered to be low by both independent reviewers in 303 (60.2%), 250 (49.7%), and 108 (21.5%) patients based on Well’s criteria, YEARS criteria, and the revised Geneva score, respectively. D-dimer testing was conducted in less than half of patients with low clinical probability [Well’s:(43.2%), YEARS:(49.7%), Geneva:(46.3%)]. Based on Well’s criteria, of 69/131 patients (52.7%) with a D-dimer < 500 ng/ml, 3/69 (4.3%) were diagnosed with PE. As per YEARS criteria, of 51/100 patients (51%) with a D-dimer < 500 ng/ml, 3/51 (5.9%) were diagnosed with PE. Based on the revised Geneva score, of 26/50 (52%) patients with a D-dimer of < 500 ng/ml, 1/26 (3.8%) patient was diagnosed with PE. All PEs were subsegmental.

Conclusion:
Many patients underwent CTPA despite having a low probability of PE due to suboptimal utilization of validated diagnostic predictive tools with D-dimer. Using a D-dimer cut-off of <500 ng/ml in patients with a low probability of PE would have missed only a small number of subsegmental PE.
Abstract 10310: Sudden Cardiac Death in Recently Diagnosed Patients With Light-Chain Cardiac Amyloidosis
Authors: Marcus Mason , Roth Lori , Sannareddy Aishwarya , Kaur Gurbakhash , Anderson Larry D , Grodin Justin L , Link Mark S
Published: June 2023

Introduction:
Untreated, light-chain (AL) cardiac amyloidosis is associated with a median survival of 6-months when diagnosed in advanced stage. However, current plasma cell-targeting therapies have drastically improved end-organ function and life expectancy. Yet, a portion still die despite appropriate treatment. We hypothesize this is from sudden cardiac death (SCD).

Aim:
To determine the incidence of and clinical characteristics associated with 90-day SCD after diagnosis of AL amyloidosis.

Methods:
Clinical, electrocardiographic, imaging, treatment, and outcomes were abstracted from consecutive patients diagnosed with AL amyloidosis from 2014-2022 at UT Southwestern Medical Center. Statistics were reported as mean and standard deviation.

Results:
In our study cohort (N=189) patients with AL amyloidosis, 18 patients (66% male, age 65 ± 9.5 y) died by 90-days (9.5%). Of these, 14 patients died by 60-days (7.3%), and 10 patient died by 30-days (5.2%). There were 7 cardiac deaths (3.6%): including one PEA arrest (0.5%), one in-hospital cardiac arrest (0.5%) and five unwitnessed out-of-hospital cardiac arrests (2.6%). Among cardiac deaths, 3 patients had endomyocardial tissue consistent with AL. Revised Mayo Stage was 66% III, 33% IV. Six patients had at least one dose of chemotherapy with bortezomib, cyclophosphamide and dexamethasone (CyBorD), Velcade/Dexamethasone, or Daratumumab/CyBorD, and 5 had at least one full cycle. The LVEF was 48.9 ± 8.1, QTc 483 ± 50 ms, interventricular septal thickness was 1.2 cm ± 0.4 cm. CMR was obtained in 4 of 7 patients, with late gadolinium enhancement present in a diffuse pattern in 75%, average LVEDV 59 ± 9.5 mL. Mean time to death was 37.2 ± 21 days.

Conclusions:
Sudden cardiac death may be a significant contributor to mortality among patients with newly diagnosed AL amyloidosis. These observations warrant confirmation in larger cohorts and may identify an unmet need to enhance risk stratification for SCD in this population.
Abstract 10312: Meta-Analysis of Influenza Vaccine and Cardiovascular Outcomes
Authors: Al-Abdouh Ahmad , Abusnina Waiel , Mhanna Mohammed , jabri ahmad , Abu Rmilah Anan , Ahmed Taha , Alabduh Taqwa , Zaalouk Mostafa , Michos Erin D
Published: June 2023

Introduction:
Influenza infection is associated with increased cardiovascular morbidity and mortality. Many observational and clinical trials suggested that influenza vaccine can reduce cardiovascular outcomes.

Methods:
We searched EMBASE, PubMed, and Cochrane Library (inception through May 24th, 2022) for randomized controlled trials (RCTs) evaluating influenza vaccine and its association with cardiovascular outcomes. We used Mantel-Haenszel method with Paule-Mandel estimator of tau2 and Hartung-Knapp-Sidik-Jonkman adjustment (due to the small number of the included studies) to calculate the risk ratio (RR) and 95% confidence interval (CI).

Results:
Eight RCTs with a total of 14,420 patients were included in our analysis. Influenza vaccine as compared with control/placebo was associated with significantly lower risk of major adverse cardiovascular events (MACE) at follow-up [RR: 0.75; 95%CI: 0.57; 0.97; I2:56%] [Figure]. There was no significant difference between influenza vaccine and placebo/control in terms of all-cause mortality [RR: 0.84; 95%CI: 0.54; 1.33; I2:50%], cardiovascular mortality [RR: 0.77; 95%CI: 0.39; 1.50; I2:57%], or myocardial infarction [RR: 0.75; 95%CI: 0.52; 1.10; I2:0%].

Conclusion:
Our meta-analysis suggests that influenza vaccine compared with control/placebo was associated with lower rates of MACE without a significant difference in the mortality or myocardial infarction rates.
Abstract 10336: Phase 3 Anticancer Agent, RRx-001, Ameliorates Hypoxia-Induced Pulmonary Hypertension
Authors: Cabrales Pedro , Reid Tony , Caroen Scott , Oronsky Bryan
Published: June 2023

Introduction:
The hallmark features of pulmonary artery hypertension (PAH), for which hypoxia is a trigger, are vascular remodeling, elevated pulmonary blood pressure, oxidative stress, and right ventricular hypertrophy. RRx-001 is a minimally toxic Phase 3 anticancer agent with anti-oxidative, anti-inflammatory, nitric oxide-donating, and anti-proliferative properties. This study aimed to investigate the effect of RRx-001 on intermittent hypoxia-induced PAH in rats.

Hypothesis:
RRx-001 attenuates PAH

Methods:
Male Wistar rats (180-220 g) were divided into four groups (n=6 per group): normoxic control, hypoxic with vehicle treatment (2 weeks breathing an atmosphere containing 10% oxygen), hypoxic treated with oral endothelin-1 receptor inhibitor, bosentan, 50 mg/kg per day for 2 weeks during hypoxia and one intravenous dose of 5mg/kg RRx-001 given the day before the start of the hypoxia. After sacrifice, hearts and lungs were removed and harvested for analyses.

Results:
RRx-001 and bosentan, separately, significantly attenuated hypoxia-induced increases in right ventricular systolic pressure and right ventricular hypertrophy in PAH rats vs. vehicle. RRx-001 and bosentan, separately, also significantly decreased the thickening of pulmonary artery media and decreased the muscularization of pulmonary arterioles in PAH rats and the wall thickness/external diameter ratio of the pulmonary arteries vs. vehicle.
Conclusions:
RRx-001 significantly reduced right ventricular systolic pressure and pulmonary remodeling in a rat model of PAH, which potentially makes it a new therapeutic option for this dread disease. As a next step, combination of RRx-001 and bosentan will be attempted.
Abstract 10357: Pyruvate Dehydrogenase Kinase 4 is a Novel Regulator of Endothelial Cell Mitochondrial Respiration in Diabetes-Impaired Angiogenesis: Implications for Preventing Diabetic Vascular Complications
Authors: Primer Khalia R , Tan Joanne T , Psaltis Peter J , Bursill Christina A
Published: June 2023

Introduction:
Diabetic patients have a greater risk of experiencing chronic wounds and amputation than non-diabetic patients. Ischaemia-driven angiogenesis is essential for tissue repair but is impaired in diabetes due to aberrant endothelial cell (EC) responses to ischaemia. Pyruvate dehydrogenase kinase 4 (PDK4) normally suppresses mitochondrial respiration in ischaemia by phosphorylating the pyruvate dehydrogenase complex (pPDC) to preserve EC function. However, the role of the PDK4/PDC axis in angiogenesis and the effects of diabetes are unexplored.

Methods and Results:
In human coronary artery endothelial cells (HCAECs), siRNA-mediated PDK4 knockdown reduced tubulogenesis (49%,
P
<0.01) and migration (51%,
P
<0.01), revealing an essential role for PDK4 in angiogenesis. HCAECs were exposed to 5 or 25mM glucose for 72h and hypoxia for 6h. High glucose attenuated the induction of
PDK4
and pPDC in response to hypoxia. This was associated with an aberrant increase in mitochondrial respiration (20%,
P
<0.01), measured by the Seahorse Bioanalyser system, and impaired tubulogenesis (52%,
P
<0.001) and migration (79%,
P
<0.0001). Lentiviral overexpression of PDK4 rescued this impairment in high glucose and hypoxia. Similarly, treatment with reconstituted high-density lipoprotein (rHDL), a known proangiogenic agent, restored the induction of
PDK4
and pPDC in hypoxia and high glucose, and rescued tubulogenesis and migration. Mechanistically, rHDL increased binding of FOXO1 to the PDK4 promoter (78%,
P
<0.05), assessed by chromatin immunoprecipitation, compared to PBS controls. In a murine model of diabetic wound healing, diabetes impaired the early induction of
PDK4
and pPDC in response to wound ischaemia, and reduced wound neovessels. Topical rHDL enhanced wound
PDK4
and pPDC levels over 72h post-wounding (68-165%,
P
<0.05), and increased wound neovascularisation (62%,
P
<0.05) and wound closure (45%,
P
<0.001), compared to PBS controls.

Conclusion:
PDK4 is essential for hypoxia-driven angiogenesis. This response is impaired in diabetes and can be corrected by PDK4 overexpression and rHDL. We have identified a novel regulatory pathway for diabetes-impaired angiogenesis that can be targeted to prevent diabetic vascular complications.
Abstract 10384: Impact of Preexisting Pulmonary Hypertension on Outcomes in Patients Hospitalized With Covid-19
Authors: Louis David , Sheikh Wasiq , Saad Marwan , Has Phinnara , kennedy kevin , Aronow Herbert D , Choudhary Gaurav
Published: June 2023

Introduction:
Pulmonary hypertension (PH) is commonly associated with cardiopulmonary co-morbidities that increase morbidity and mortality risk with COVID-19.

Hypothesis:
This study aims to evaluate the association between preexisting PH and in-hospital outcomes in patients admitted with COVID-19.

Methods:
Consecutive patients at a large New England academic health system hospitalized with COVID-19 between March 1 and December 31, 2020, who had prior echocardiograms with documented estimated right ventricular systolic pressure (RVSP) were included. PH was defined as RVSP ≥30 mm Hg. Multivariable logistic regression adjusting for demographic and clinical characteristics was employed to relate PH to a primary outcome of all-cause mortality, and secondary outcomes including non-invasive positive pressure ventilation (NIPPV), myocardial infarction (MI), intensive care unit admission (ICU), and recurrent heart failure (HF) individually.

Results:
Of the 656 patients admitted, 395 (60.2%) had documented PH on a prior echocardiogram. PH patients were older, more likely to be men, and have cardiopulmonary and renal disease. Patients with PH had larger atrial size and higher E to early diastolic mitral annular tissue velocity (E/e') but similar left ventricular and right ventricular function compared to patients without PH. All-cause mortality (21% vs 10.3%, p= 0.001), need for ICU level of care (19% vs 13%, p = 0.046), NIPPV (23% vs 16%, p = 0.03), and recurrent HF (18% vs 5%, p < 0.001) were more common in patients with PH compared to those without. Unadjusted and adjusted odds ratios relating PH to study outcomes appear in the
Table
.

Conclusions:
Preexisting PH is independently associated with higher risk of all-cause mortality in patients who are hospitalized with COVID-19.
Abstract 10387: Macrophage Migration Inhibitory Factor Maintains Mitochondrial Integrity in Aging During Ischemic Insults
Authors: Wang Hao , Zoungrana Linda Ines , Li Zehui , Iglesias Migdalia , Davitt Kayla , Fatmi Mohammad , Krause-Hauch Meredith , Li Ji
Published: June 2023

Introduction:
The expression and secretion of cardiac MIF (macrophage migration inhibitory factor) are downregulated in aging. A small molecule MIF agonist, MIF20 can increase the binding affinity of MIF with CD74 receptor to modulate AMPK signaling. However, the pharmacological mechanisms by which MIF20 triggers MIF-AMPK signaling cascade to benefit heart in response to ischemia and reperfusion (I/R) stress remain unknown.

Hypothesis:
MIF20 rescues an impaired MIF-AMPK signaling in aging through augmenting the interaction between MIF and CD74 receptor to maintain mitochondrial integrity of aged heart under ischemic stress.

Methods:
Young (3-5 months) and aged (21-24 months) C57BL/6J mice were subjected to 45 min of ligation of LAD (left anterior descending coronary artery) and injection of MIF20 (0.15 μg/kg, i.v.) 5 min before 24 hr of reperfusion with release of LAD. Echocardiography measures cardiac functions, and TTC/Evans blue staining for determination of myocardial infarction size. Seahorse XF Analyzer for mitochondrial respiration functions of isolated cardiomyocytes.

Results:
The echocardiography data showed that I/R caused cardiac systolic dysfunctions but not effect on cardiac diastolic functions of both young and aged C57BL/6J mice. There were no differences between male and female groups. Administration of MIF20 significantly ameliorated I/R-induced cardiac dysfunctions in both young and aged mice, while more improvement observed in aged versus young mice. MIF20 treatment reduced myocardial infarct size caused by I/R in both young and aged mice, but the reduction extent of aged hearts was higher than that of young hearts (p<0.05). Mitochondrial respiration rates of isolated cardiomyocytes as indicted by ATP production were impaired by I/R versus sham operations in both young and aged hearts. Intriguingly, MIF20 treatment significantly rescued the impaired mitochondrial functions caused by I/R in both young and aged cardiomyocytes. Moreover, the mitochondrial functions of young and aged cardiomyocytes were improved to a similar level under I/R with MIF20.

Conclusions:
MIF agonist MIF20 rescues the impaired energy metabolism in aged heart. The mitochondrial integrity under I/R by MIF20 could limit ischemic insults in aging.
Abstract 10395: Atherosclerotic Lesion in Chronic Thromboembolic Pulmonary Hypertension is Associated With Prolonged Symptom Duration
Authors: Liu Jixiang , Chang Ziyi , Zhang Zhu , Li Yishan , Zhen Kaiyuan , Tian Han , Xie Wanmu , Yang Peiran B , Zhai Zhenguo
Published: June 2023

Background:
The cause of atherosclerotic lesions in the pulmonary artery of patients with chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We aimed to discuss the clinical characteristics of CTEPH patients with atherosclerotic lesions and further explore the unique metabolic pathway of atherosclerosis in the pulmonary artery.

Methods:
Following detailed pathological examination of the pulmonary endarterectomy (PEA) specimen, CTEPH patients were divided into two age- and sex-matched groups, those with and without atherosclerotic lesion (n=25 each), and their clinical characteristics were compared. Untargeted metabolomics were used to determine the different metabolites in the proximal lesions of the pulmonary artery.

Results:
27.2% (25/92) of all PEA specimens were found with atherosclerotic lesions. Patients with atherosclerotic lesions were more likely to have a history of symptomatic embolism than those without atherosclerotic lesion (88% vs. 56%, P=0.012), including pulmonary embolism and deep venous thrombosis. Patients with atherosclerotic lesions were found to have longer symptom duration (8.0±6.5 vs. 4.7±4.2, P=0.039) and a lower rate of residual pulmonary hypertension after PEA than those without atherosclerotic lesion (40% vs. 56%). However, the existence of atherosclerotic lesion was not associated with pre-operative hemodynamic parameters and cardiac function. Metabolomic profiling revealed that the formation of atherosclerotic lesion in CTEPH is closely related to glycine, serine and threonine metabolic axes involved in cellular aging and energy metabolism.

Conclusions:
The occurrence of atherosclerotic lesions in the pulmonary artery of CTEPH was associated with symptomatic thromboembolic history and extended symptom duration. The results suggested a new link between atherosclerotic lesions and aberrant amino acid metabolism in the context of CTEPH. Further investigations focused on atherosclerotic lesion and pulmonary vascular remodeling may provide novel insight into the pathophysiology and new therapeutic strategies for CTEPH.
Abstract 10408: Insulin Resistance in Type 2 Diabetes is Moderated by Saturated Fatty Acids
Authors: Mezincescu Alice M , Rudd Amelia , Cheyne Lesley , Horgan Graham , Philip Sam , Cameron Donnie , van Loon Luc , Whitfield Philip , Gribbin Rachael , Delibegovic Mirela , Fielding Barbara , Gray Stuart , Henning Anke , Dawson Dana K
Published: June 2023

Background:
Increased intramyocellular lipid storage occurs in skeletal muscle of both athletes and type 2 diabetes patients (T2D) but their metabolic phenotypes are at opposite ends of insulin sensitivity and cardiometabolic risk.

Hypothesis:
Intramyocellular lipid saturation and flux are determinants of insulin resistance.

Methods:
Age-matched athletes (n=28) and T2D (n=27) underwent
1
H-magnetic resonance spectroscopy for analysis of saturated (fSL) and unsaturated lipid (fUL) fractions of vastus lateralis, blood lipids, glucose and insulin sensitivity, skeletal muscle biopsy for lipidomics/insulin signalling, cardiopulmonary exercise peak VO
2
and intravenous administration of stable isotopes of [U-
13
C]-palmitate and -linoleate for skeletal muscle saturated/unsaturated fatty acid fluxes (fractional synthesis rate, FSR). Tests were performed at baseline and after controlled insulin sensitivity changes (4-week athletes deconditioning and endurance exercise training at ≥65% of baseline peakVO
2,
5 hours/week x 8 weeks in T2D).

Results:
We demonstrate higher intramyocellular fSL and lower fUL in athletes compared to T2D (p=0.0004). Trained athletes have a 4-fold (palmitate) and 2.2-fold (linoleate) higher FSR compared to T2D (p=0.005 and 0.006, respectively). Athletes’ deconditioning results in reductions in skeletal muscle lipid saturation, palmitate and linoleate FSR. Conversely, 8-week endurance training of T2D results in intramyocellular lipid saturation increase (p<0.0001) as well as a relatively larger (2.2-fold) palmitate FSR increase (p=0.04) than the 1.8-fold linoleate FSR increase (p=0.03), re-aligning the T2D skeletal muscle phenotype to that of deconditioned athletes. These adaptations were synchronous with significant insulin sensitivity improvement (p<0.05), decrease in serum cholesterol (p=0.02) and triglycerides (p=0.0005), improved glycaemic control (HBA1c, p=0.0003), increased peak VO
2
(p<0.0001)

and upregulation of skeletal muscle phosphorylated AKT (p=0.01) and AMPK (p=0.005) in T2D.

Conclusions:
Maladapted intramyocellular lipid storage and fluxes in T2D patients show reversibility after endurance training through increased contributions of the saturated fatty acids pools.
Abstract 10410: Association Between Coronary Artery Calcium Scoring With Statin Initiation, Cholesterol Reduction and Cardiovascular Outcomes in Black Patients
Authors: Wilgor Abigail , Dong Tony , Tashtish Nour , Hackler Eddie , Neeland Ian , Rajagopalan sanjay , Al-Kindi Sadeer
Published: June 2023

Introduction:
Coronary artery calcium (CAC) scoring is a cost-effective and reproducible method to assess risk for cardiovascular (CV) outcomes and is particularly important for guiding prevention in asymptomatic patients. Black patients are at high risk for atherosclerotic cardiovascular disease (ASCVD) that is not fully explained by traditional risk factors. In this study, we investigated the prevalence of CAC and its association with CV events in Black and white individuals.

Methods:
We investigated the baseline characteristics, rates of statin initiation, changes in cholesterol, and major adverse CV events (myocardial infarction, stroke, death) in 49,799 patients with self-reported race (Black or white) who underwent CAC scoring in the CLARIFY study between 2014 and 2020 (Clinicaltrials.gov NCT04075162).

Results:
In total, there were 4,292 Black patients and 45,507 white patients. Compared with white patients, Black patients had similar age (P=0.17), were more likely to be female (60.5% vs 50%, P<0.001), had higher 10-year ASCVD risk by pooled cohort equation (16.18% vs. 11.06%, P<0.001), lower LDL cholesterol (115 vs 123 mg/dL, P<0.001), and were more likely to have CAC of 0 (49.2% vs 39.9%, P<0.001). At every 10-year ASCVD risk category by pooled cohort equation, CAC was more prevalent in white patients than Black patients (p<0.001). Despite similar statin initiation post CAC score in patients not on statins at baseline, Black patients had less relative reduction in LDL cholesterol over 1 year compared with white patients (figure). Within each CAC category, Black patients had higher rates of CV events (P<0.003) over 1 year.

Conclusions:
In this large cohort of patients undergoing CAC scoring, Black individuals had lower CAC scores despite having higher predicted ASCVD risk and worse outcomes. Black individuals had less relative reduction in cholesterol over 1 year compared with white individuals, despite having similar statin initiation rates.
Abstract 10411: Low Rate of Major Adverse Cardiovascular Events in Patients Presenting to Urgent Care With Chest Pain and a Moderate HEART Risk Score Who Were Referred for an Expedited Outpatient Cardiology Evaluation
Authors: Barbarash Svetlana , Lebron-Gallagher Dolores , Julson Hollis , Weinstock Michael
Published: June 2023

Introduction:
The HEART score is an effective method of risk stratifying emergency department (ED) patients with chest pain. The low rate of major adverse cardiovascular events (MACE) in patients with a moderate risk HEART score referred from an urgent care (UC) center for an expedited outpatient cardiology evaluation was first described by this group in 2020. This is a follow up study with a total of 446 patient over a 36 month period.

Hypothesis:
Patients with a moderate risk HEART score who present to the ED are usually hospitalized for further evaluation. The safety of outpatient evaluation of these patients is not well studied. We assessed the hypothesis that there is a low rate of MACE when patients with a moderate risk HEART score were referred from an UC for an expedited outpatient cardiology follow up.

Methods:
A cross sectional study was performed from 2/14/2019 through 3/30/2022 in 5 UC centers of 446 patients who presented with chest pain or anginal equivalent and a HEART score of 4 to 6 in Las Vegas, Nevada. A streamlined disposition protocol was adopted by all UC providers for an expedited outpatient cardiology instead of ED referral. The population was followed for 6 weeks with a primary endpoint of MACE (death, myocardial infarction (MI), revascularization) determined by electronic medical records review and direct phone contact with patients. Outcomes were confirmed in 93% of patients.

Results:
The average age was 65 years with 52% female and 48% male. 395 patients (89%) were seen by a cardiology provider, 346 patients (88%) were seen within 3 days. 265 stress tests (67%), 42 coronary CT angiograms (11%) and 19 invasive coronary angiograms (5%) were ordered. 8 patients (2%) were found to have MACE: 2 had routine surgical revascularization, 4 had non-fatal MI followed by revascularization, 2 patients died: 1 was urgently referred for mitral valve replacement and died after surgery from renal failure and COVID, the other patient died from COVID pneumonia. There were no ischemic cardiac deaths.

Conclusion:
In conclusion, patients with a moderate risk HEART score referred from UC for an expedited outpatient cardiology evaluation had a low rate of MACE and no ischemic cardiac deaths due to delay of care.
Abstract 10412: Malnutrition Severity is Associated With Worse Outcomes in Patients Admitted With Acute Myocardial Infarction
Authors: Mohamad Alahmad Mohamad Alhoda , gupta Kamal
Published: June 2023

Introduction:
Malnutrition has been associated with inferior outcomes in patients admitted with acute myocardial infarction (AMI). However, there is a lack of data to assess if the degree of malnutrition correlates with outcome severity.

Methods:
We used Nationwide Readmission Database (NRD) for 2016-2019 in our cross-sectional study. First, we extracted all cases older than 18-years that include a primary diagnosis of AMI. Appropriate survey and domain analyses were applied to obtain national estimates using SAS 9.4.

Results:
We identified 2,280,393 discharges for AMI. Malnutrition was present in 4% of the study cohort (or 89,490 cases). Half of the patients with malnutrition (or 44,919) had moderate to severe malnutrition. The other 44,371 (or 50%) had a milder degree of malnutrition. Patients with malnutrition were younger than those without malnutrition (mean age 72-years vs. 75-years, p<0.001) and had more women (48% vs. 37%, p<0.001). Patients with malnutrition had a higher prevalence of underlying heart failure, dementia, coagulopathy, and chronic (liver, renal, and lung) diseases (p<0.001). Malnourished patients also had significantly higher inpatient mortality (12.5% vs. 4.6%, p<0.001), length of stay (mean of 13 days vs. 7 days, p<0.001), and all-cause 30-day readmission rates (19% vs. 13%, p<0.001). Inpatient mortality on readmission was also higher in those with malnutrition (2% vs. 0.6%, p<0.001). Univariate analysis showed that the severity of malnutrition also correlated with higher inpatient mortality (OR 2.34[2.24-2.46] for mild malnutrition and 3.65[3.49-3.82] for advanced malnutrition). After adjusting for age, gender, heart failure, dementia, coagulopathy, chronic (liver, renal, and lung) diseases, and history of cardiovascular revascularization presence of malnutrition and severity of malnutrition continued to be associated with higher inpatient mortality compared to those without malnutrition (OR 1.20[1.14-1.26] for mild malnutrition and OR 1.69[1.61-1.78] for more severe malnutrition).

Conclusions:
In patients hospitalized with AMI, underlying malnutrition is associated with worse outcomes. The severity of malnutrition also correlates with worse outcomes.
Abstract 10419: Mechanical Properties of Flap and Adventitia in Type B Aortic Dissection
Authors: Dong Hai , Liu Minliang , Zhou Yumeng , Chhabra Arshiya , Oshinski John N , Sun Wei , Elefteriades John A , Leshnower Bradley G , Gleason Rudolph L
Published: June 2023

Introduction:
Type B Aortic Dissection (TBAD) is a lethal disease. The tissue mechanical property is of great importance for estimating TBAD rupture risk. This study sought to characterize the mechanical properties of stiffness and strength of dissection flap and adventitia tissues from patients with chronic TBAD.

Methods:
Aortic tissue removed from 23 patients undergoing open repair of thoracoabdominal aortic aneurysms secondary to chronic TBAD was analyzed. Uniaxial testing was performed on the flap (circumferential [Circ] n=11, axial n=8) and on the adventitia (Circ n=7, axial n=6 ). The uniaxial lower tangent modulus (uLTM), uniaxial higher tangent modulus (uHTM) and ultimate tensile strength (UTS) were obained for each sample from stress-strain relation (Fig. 1a). We also perfromed biaxial tension testing (BTT, in Circ and Axial) of the flap (n=7) and adventitia (n=9). BTT is closer to the
in vivo
loading condition than uniaxial testing. Since BTT usually achieves lower maximum stress, here only the biaxial lower tangent modulus (bLTM, Fig. 1b) was obtained.

Result:
The uLTM of the dissection flap (Fig. 1c), and bLTM of the flap and adventitia (Fig. 1d) in Circ are significantly larger than those in Axial (p=0.006, 0.011, and 0.008, repsectively). In Circ (Fig. 1d), the bLTM of the adventitia is larger than that of the flap (p=0.027). The flap UTS in Circ is larger than that in Axial (Fig. 1f, p<0.001). In Axial, adventitia UTS is larger than flap UTS (Fig. 1f, p=0.001).

Conclusions:
The adventitia is stiffer and stronger than the dissection flap in patients with cTBAD. These biomechanical data corroborate the surgical axiom of including the adventitia in surgical repair of aortic dissections. Furthermore, the flap and adventitia in Circ are stiffer than those in Axial. These findings may provide insight into the ability of the aorta to maintain its wall integrity in the setting of hypertension and aneurysmal disease, and provide foundations for estimating the risk of TBAD.
Abstract 10421: Factors Associated With Early and Late Restenosis Following Drug-Coated Balloon Treatment for Patients in Femoropopliteal Lesions
Authors: Toyoshima Taku , Iida Osamu , Asai Mitsutoshi , masuda masaharu , Okamoto Shin , Ishihara Takayuki , Nanto Kiyonori , Tsujimura Takuya , Matsuda Yasuhiro , Hata Yosuke , Uematsu Hiroyuki , Higashino Naoko , Nakao Sho , Tsukizawa Tomofumi , Fujihara Masahiko , Nishian Kunihiko , KAWASAKI DAIZO , Takahara Mitsuyoshi , Mano Toshiaki
Published: June 2023

Introduction:
Drug-coated balloon (DCB) improves clinical outcomes and has created a paradigm shift in the treatment of femoropopliteal (FP) lesions. However, in real-world FP practice, we occasionally experience early restenosis after DCB treatment despite the achievement of angiographic success at initial endovascular treatment (EVT). The objectives of this study was to elucidate factors associated with early (within 6-month) and late restenosis (after 6-month) following DCB treatment for real-world FP lesions.

Methods:
This was a multicenter and retrospective study enrolling 486 lesions (lesion length: 12±10 cm, chronic total occlusion [CTO]: 21%, involving popliteal arterial lesions: 43%) in 423 patients (age: 74±9 years, female: 29%, diabetes mellitus: 61%, hemodialysis: 38%, chronic limb-threatening ischemia: 42%) who underwent EVT using DCB between January 2018 and December 2019 in three cardiovascular centers. The outcome measure was primary patency, and the predictors of early and late restenosis were explored by cox proportional regression analysis.

Results:
During the mean observation period of 25.3±12.1 months, primary patency at 6-, 12-, 24-, and 36-month was 93.1%, 79.1%, 61.6%, and 48.7%, respectively. A total of 31 lesions and 138 lesions developed early and late restenosis, respectively. Multivariate analysis revealed that CTO lesion (Hazard ratio [HR]: 2.29, p=0.033) and involving ostial lesion of superficial femoral artery (HR: 2.73, p=0.009) were significantly associated with early restenosis, while calcification angle over 270° (HR: 1.66, p=0.005), smaller distal external elastic membrane (EEM) diameter evaluated by intravascular ultrasound (HR: 1.03, p< 0.001) and involving popliteal arterial lesions (HR: 1.53, p=0.018) were significantly associated with late restenosis.

Conclusions:
The factors associated with early restenosis following DCB treatment for real-world FP lesions differed from those with late restenosis.