bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13732: Left Ventricular End Diastolic Pressure in Women With Ischemia and No Obstructive Coronary Artery Disease: An Analysis From the Women's Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction Study
Authors: Tjoe Benita , Bairey Merz C N , Cook-Wiens Galen , Anderson David , Petersen John W , Samuels Bruce , Nelson Michael , Shufelt Chrisandra , Handberg Eileen M , Pepine Carl , Wei Janet
Published: April 2024

Introduction:
Coronary microvascular dysfunction (CMD) has been proposed as a pathophysiological mechanism in heart failure with preserved ejection fraction (HFpEF). Elevated left ventricular end-diastolic pressure (LVEDP) is often present in patients with CMD.

Hypothesis:
We hypothesized that CMD-mediated impairment in LV relaxation may contribute to elevated LVEDP.

Methods:
Women (n=253; age 53.6 ± 11.5) with signs and symptoms of ischemia and no obstructive coronary artery disease underwent invasive coronary functional testing (CFT) for measurement of resting LVEDP, coronary flow reserve to adenosine, change in coronary blood flow and coronary artery diameter to acetylcholine, and diameter change to nitroglycerin. A subset (n=208) had rest-stress CMR at mean 47 days from CFT. Two sample t-test, Fisher’s exact test and Spearman correlation were performed.

Results:
All women had normal LVEF and no significant valvular disease. Mean LVEDP was 14.4±5.0 mmHg, with 150 women (59%) having LVEDP >12 mmHg. Comorbidities and medications were similar between groups (
Table
). LVEDP correlated with body mass index (BMI) (r=0.324, p<0.001), systolic (r=0.176, p=0.01) and diastolic systemic blood pressure (r=0.13, p=0.059) at time of CFT, as well as with time to peak filling rate (r=0.13, p=0.050), a CMR measure of diastolic function. LVEDP did not relate to invasive CFT measures nor CMR myocardial perfusion reserve index. LVEDP also did not correlate with CMR measures of LV function or structure, adjusted for body-surface area.

Conclusions:
Among women with suspected CMD, elevated resting LVEDP is prevalent and associated with higher BMI and systemic blood pressure. There were no significant associations between LVEDP and measurements of CMD in this cross-sectional analysis. Further analyses are underway to evaluate whether raised LVEDP initially from hypertension and obesity may lead to CMD, myocardial ischemia, structural impairment and development of HFpEF.
Abstract 13736: Trends and Disparities in Mortality Rates From Acute Myocardial Infarction in United States Cancer Patients
Authors: Vuong Jacqueline T , Ziaeian Boback , Yang Eric H
Published: April 2024

Introduction:
Cardiovascular disease and cancer are major causes of morbidity and mortality in the United States. Risk of acute myocardial infarction (AMI) is elevated in cancer patients, which may be due to shared risk factors as well as the cardiotoxicity of oncologic therapies. This study aims to estimate the mortality burden from AMI in the United States cancer population and identify demographics of affected populations.

Methods:
Data were obtained from the multiple causes of death data files from CDC WONDER from 1999-2019. All deaths with ICD 10 code I21 for “acute myocardial infarction” listed as the underlying cause of death and ICD-10 codes C00-C97 for “malignant neoplasms” listed as a contributing cause of death were included. Age-adjusted mortality rates (AAMR) were calculated based on the 2000 United States standard population.

Results:
There were 98,414 deaths from AMI with underlying cancer between 1999 to 2019, comprising 33.7% of all AMI deaths, with AAMR of 1.41 deaths/100,000 (95% CI 1.40-1.42). Mortality rates were higher in men (2.18/100,000; 95% CI 2.16-2.20) than women (0.90/100,000; 95% CI 0.89-0.91); relative risk 2.42. Among racial groups, African Americans had the highest mortality rate 1.66/100,000 (95% CI 1.62-1.69). In overall demographics, African American males have the highest mortality rate, 2.66 deaths/100,000 (95% CI 2.59-2.73), followed by White American males (2.19 deaths/100,000 (95% CI 2.17-2.20). African American women had higher mortality rates than women of any other racial group (1.09 deaths/100,000 95% CI 1.06-1.13)
(Figure).

Conclusions:
Cancer patients make up a significant portion of all deaths from AMI. Africans Americans and males are disproportionately affected, and efforts should be made to elucidate the pathophysiologic and socioeconomic explanations for these disparities.
Abstract 13743: Prevalence of Cardiac Rhythm Disturbances in Heart Failure Patients With and Without Cardiac Amyloidosis: A National Inpatient Sample Analysis
Authors: Atluri Ramtej , Yalamanchili Sreeram , Kodali Mouna , Shrestha Prajwal , Kang Cyra
Published: April 2024

Background:
Cardiac amyloidosis (CA) is well-known to affect electrocardiographic findings. However, the impact of CA on the prevalence of cardiac arrhythmias, particularly in heart failure (HF) patients, is unknown. Our aim was to assess the prevalence of arrhythmias in HF patients with and without CA.

Methods:
A retrospective cohort study was conducted using the Nationwide Inpatient Sample from 2017. About 5,074,059 patients who had acute, acute on chronic and chronic HF as primary or secondary diagnosis were identified and stratified based on the presence or absence of CA using ICD-10 codes. Both univariate regression and literature review were used to determine the covariates. Multivariate logistic regression analysis was used to adjust for confounders and analyze the variables.

Results:
Out of the 5,074,059 hospitalized patients with a primary and secondary diagnosis of HF, 7,980 individuals had CA. HF patients with CA had a higher prevalence of Atrial Fibrillation (AF) (52.6% vs 39.3%), Atrial Flutter (AFL) (9.4% vs 3.89%), Ventricular tachycardia (VT) (9.6% vs 4%), Supraventricular tachycardia (SVT) (3.9% vs 2.1%), right bundle branch block (RBBB) (2.9% vs 1.6%), 1st degree AV block (1AVB) (3.07% vs 1%), 2nd degree AV block (2AVB) (1.4% vs 0.4%), and 3rd degree AV block (3AVB) (1.25% vs 0.7%) than without. When adjusted to patient demographics, comorbidities, and hospital characteristics, HF patients with CA had higher risk of AF (aOR= 1.67, p<0.0001), AFL (aOR=2.9, p<0.0001), VT (aOR=2.08, p<0.0001), SVT (aOR=1.63, p<0.0001), RBBB (aOR=1.62, p=0.002), 1AVB (aOR=2.27, p<0.0001), and 2AVB (aOR=2.86, p<0.0001) compared to those without. However, there was no significant difference in the prevalence of Ventricular Fibrillation (VF) (aOR=0.92, p=0.82) in the same population.

Conclusion:
HF patients with CA are 67%, 190%, 108%, 63%, 62%, 127%, and 186% more likely to develop AF, AFL, VT, SVT, RBBB, 1AVB, and 2AVB respectively, than those without. However, HF patients with CA did not have a significant difference in the prevalence of VF, 3AVB, and LBBB. CA is an infiltrative disease process that is known to cause cardiac conduction disturbances. Limitations include the underdiagnosis of CA in our society as well as the non-specificity of ICD codes for CA.
Abstract 13798: Pulmonary Arterial Hypertension Associated With Repaired Congenital Heart Disease in Children: Comparable Survival to Eisenmenger Syndrome
Authors: Constantine Andrew , Dimopoulos Konstantinos , Clift Paul , Condliffe Robin , Jansen Katrijn , Muthurangu Vivek , Moledina Shahin
Published: April 2024

Introduction:
Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD). Advances in management have altered the demographics of PAH-CHD, with fewer cases of Eisenmenger syndrome (ES) and more patients with PAH after CHD repair, who have worse outcomes than ES patients and an idiopathic PAH (IPAH)-like phenotype. However, pediatric data are limited.

Methods:
Patients under active follow-up in the National Paediatric Pulmonary Hypertension service UK between 2001 and 2021 were identified. Incident patients were included in survival analysis.

Results:
Overall, 164 patients with repaired PAH-CHD were included (57.9% female, 53.7% trisomy 21, 3.7[0.1-16.8] years at diagnosis), along with 95 patients with ES and 146 with IPAH. Most repaired PAH-CHD patients had an isolated post-tricuspid (59%), followed by a combined pre/post-tricuspid (28%) and isolated pre-tricuspid shunt (13.4%). Median age at repair was 13.6[5.6-51] months.

PAH was diagnosed prior to repair in 24.5%. Symptoms were present in 53.7%, whereas 46.3% were identified during surveillance. PAH therapy was started in 86%; at last follow-up, repaired PAH-CHD patients were less likely to be on combination therapy than IPAH patients (32.9% vs 70.5%, p<0.0001). Resolution of PH occurred in 8.5% patients at 6.4[3.1-9.4] months from diagnosis.

Transplant-free survival in repaired PAH-CHD was 91.9% (95%CI: 87.6-96.4%) at 1 year, 86.1% (80.4-92.2%) at 5 years, and 77% (68.2-86.9%) at 10 years. Repaired PAH-CHD diagnosed in infancy had a significantly worse survival (
Fig 1A
). There was no difference in survival between repaired PAH-CHD and ES (p=0.68). IPAH had a worse survival than both groups (HR vs repaired 1.97, 95%CI:1.22-3.2, p=0.006,
Fig 1B
).

Conclusions:
In this national paediatric cohort, patients with PAH after CHD repair had a better prognosis than patients with IPAH and similar to ES, albeit with a 23% mortality at 10 years, worse in patients diagnosed as infants.
Abstract 13862: Appropriate Therapy in the Subcutaneous and Transvenous ICD: A Secondary Analysis of the PRAETORIAN Trial
Authors: Knops Reinoud , van der Stuijt Willeke , Delnoy Peter Paul , Boersma Lucas V , Kuschyk Juergen , El-Chami Mikhael F , Bonnemeier Hendrik , Behr Elijah R , Brouwer Tom F , Kaab Stefan , Mittal Suneet , Quast Anne-Floor B , Smeding Lonneke , De Weger Anouk , Bijsterveld Nick , Richter Sergio , Brouwer Marc , de Groot Joris R , Kooiman Kirsten , Lambiase Pier , Neuzil Petr , Vernooy Kevin , Alings Marco , Betts Tim , Bracke Frank , Burke Martin C , de Jong Jonas S , Wright David , Jansen Ward P , Whinnet Zachary I , Nordbeck Peter , Knaut Michael , Philbert Berit Thornvig , Van Opstal Jurren M , Chicos Alexandru , Allaart Cornelis , Borger van der Burg A.E. , Clancy Jude f , Dizon Jose , Miller Marc , Nemirovsky Dmitry , Surber Ralf , Upadhyay Gaurav A , Weiss Raul , Tijssen Jan G , Olde Nordkamp Louise R , Wilde Arthur A ,   PRAETORIAN investigators
Published: April 2024

Introduction:
The randomized PRAETORIAN trial demonstrated non-inferiority of the subcutaneous implantable cardioverter-defibrillator (S-ICD) compared to the transvenous ICD (TV-ICD) with regard to inappropriate shocks and complications. Due to its extrathoracic position, the S-ICD lacks the possibility to provide antitachycardia pacing (ATP) which might result in more appropriate shock therapy. In this pre-specified secondary analysis, we aim to compare first occurrence of appropriate therapy in the S-ICD and TV-ICD.

Methods:
The PRAETORIAN trial is an international, multicenter, randomized trial (NCT01296022) in which 849 patients with a class I or IIa indication for ICD therapy and without the need for pacing were randomized in a 1:1 ratio to receive either an S-ICD (n = 426) or a TV-ICD (n = 423). Analyses were performed in the modified intention-to-treat population, which included patients according to the group to which they had been randomly assigned regardless of the device they received, but excluded patients who did not receive any ICD.

Results:
At a median follow-up of 49.1 months, 164 patients received appropriate therapy, of whom 86 in the S-ICD group and 78 in the TV-ICD group (48-month Kaplan-Meier estimated cumulative incidence 19.4% and 17.5%, respectively; hazard ratio 1.12; 95%CI, 0.83 to 1.53; p=0.45). In 83 patients (97%) in the S-ICD group the first arrhythmia was treated with a shock and in 3 patients (3%) with ATP. In 25 patients (32%) in the TV-ICD group the first arrhythmia was treated with a shock, in 31 patients (40%) solely with ATP and in 22 patients (28%) with ATP followed by a shock.

Conclusions:
In this secondary analysis of the PRAETORIAN trial, we found no statistical difference in first occurrence of appropriate therapy in the S-ICD group and TV-ICD group. Due to ATP, patients were less often treated with shocks in the TV-ICD group. A further analysis of all appropriate therapy in the PRAETORIAN trial could reveal the true benefit of ATP.
Abstract 13892: The Impact of Cardio-Renal Comorbidities on Medical Spend in Patients With Diabetes: A Contemporary Analysis of a Large Accountable Care Organization
Authors: Al-Kindi Sadeer , Neeland Ian J , Coran Justin , Hatipoglu Betul , Rahman Mahboob , Rahmani Sara , Pronovost Peter , Rajagopalan Sanjay
Published: April 2024

Introduction:
While it is well-known that Type 2 Diabetes (T2D) has a disproportionate impact on healthcare expenditure, the precise extent to which cardiorenal and mental health complications of diabetes in accountable care organizations (ACO) influence cost is not clear. We sought to investigate the association between these factors and medical spend in patients with T2D in a large ACO.

Methods:
We identified all patients (≥ 18 years) with T2D (defined as HbA1c ≥ 6.5% and by ICD10 codes) within our ACO population and linked their total medical spend (inpatient and ambulatory visits) for the year 2020. We investigated the association between medical spend and medical comorbidities (figure A), body mass index (BMI), glycated hemoglobin (HbA1c), and glomerular filtration rate (GFR).

Results:
A total of 28,566 patients with T2D were included. Mean age was 65 years, 50% were female, and 20% were Black. Comorbid conditions were common: 88% had hypertension, 33% had CAD, 19% had cerebrovascular disease, 19% had HF, 20% had CKD, 32% had OSA, 34% had anxiety, 10% had depression. Median annual spend was $754 per patient. Comorbidities associated with increased spend are shown in figure A. Patients with cardiorenal comorbidities had 723% increase in medical spend. Medical spend was weakly associated with HbA1c and BMI but increased sharply at GFR <25 ml/min/1.73 m2 (figure c). Patients with cardiorenal comorbidities accounted for 50% of all patients with T2D and 79% of the medical spend in T2D.

Conclusions:
In a contemporary large ACO population, cardiorenal comorbidities are associated with medical spend. Interventions to promote value in ACOs may need to focus on these high-risk groups.
Abstract 13937: The Association Between Left Ventricular End-Diastolic Diameter and Long-Term Mortality in Patients With Coronary Artery Disease
Authors: Li Qiang , Liu Jin , Huang Haozhang , Chen Weihua , Shi Shanshan , Chen Shiqun , Liu Yong
Published: April 2024

Background:
Left ventricular end-diastolic diameter (LVEDD) is a common indicator in echocardiogram, and increased LVEDD is correlated with left ventricular (LV) insufficiency. However, the relationship between LVEDD and mortality in patients with coronary artery disease (CAD) is uncertain.

Methods:
This study enrolled 33,147 patients with CAD who had undergone transthoracic echocardiography between January 2007 and December 2018 in Cardiorenal Improvement (CIN) study (ClinicalTrials.gov NCT04407936). These patients were divided into four groups according to the quartile of LVEDD (Quartile 1: LVEDD≤43 mm, Quartile 2: 43<LVEDD≤46 mm, Quartile 3: 4651 mm) and were categorized into two groups (Quartile 1-3 versus Quartile 4). Survival curves were generated with the Kaplan-Meier method. The restricted cubic splines and cox proportional hazards models were used to investigate the association with LVEDD and all-cause mortality.

Results:
In our study, there were a total of 33,147 patients, whose average age was 63.0±10.6 years and 24.01% of them were female. In the average follow-up period of 5.2 years, a totally of 4,288 patients died. After adjusting for confounding factors, patients with the larger LVEDD (Quartile 4) remain had a 1.19-fold risk for all-cause mortality (95% confidence interval: 1.09 to 1.30) compared with the lower quartile (Quartile 1-3).

Conclusions:
Enlarged LVEDD was an independent predictor of all-cause mortality in patients with CAD. LVEDD measurements may be helpful for risk stratification and providing therapeutic direction for the management of CAD patients.
Abstract 13978: Concomitant Mitral Valve Repair During LVAD Implantation Does Not Improve Outcomes
Authors: Shariati Farnoosh , Duran Antonio , Tutor Austin , Sleem Amber , KRIM SELIM , Desai Sapna , Eiswirth Clement C , Wever-Pinzon James , Ventura Hector
Published: April 2024

Introduction:
Significant mitral valve regurgitation (MR) is common in those with advanced heart failure and encompasses approximately half of patients who are undergoing left ventricular assist device (LVAD) implantation. LVAD can decrease the severity of MR by LV decompression, however not all patients undergoing LVAD implantation achieve optimal LV decompression. In this study, we assessed the effect of concomitant mitral valve repair (MVr) during LVAD implantation.

Methods:
Retrospective study of LVAD (HM3 devices exclusively) between 8/2015 to 7/2020 at our institution. We divided our population based on whether they underwent concomitant MVr or not at the time of LVAD implant. We compared one-year outcomes between groups. Primary endpoint was a composite outcome of HF admission and mortality. Secondary endpoints were HF admissions, mortality, and heart transplantation. In a secondary analysis, we analyzed only those patients with
>
moderate MR.

Results:
Total of 195 patients were included. Mean age at implant was 52.2, male accounted for 78.5%, non-ischemic cardiomyopathy 74.4%. Concomitant MVr was performed in 83 (43%) and no repair in 112 (57%) of patients. There were no differences in any of the primary or secondary endpoints between both groups (Table 1). Secondary analysis evaluation of only those with > moderate MR also showed no differences in outcomes at one year. (Figure 1)

Conclusion:
In a homogeneous population of HM3 LVADs, concomitant MVr was not associated with improved outcomes regardless of MR severity. Our study adds to prior literature that MVr does not have an additive benefit over LVAD unloading.
Abstract 14101: CES1 Deficiency is Associated With Oxidative Stress and Endoplasmic Reticulum/Mitochondrial Injury in Pulmonary Endothelial Cells
Authors: Agarwal Stuti , Chakraborty Ananya , Condon David , Shamskhou Elya , Patel Hiral , Liu Lichao , West James , Suresh Karthik , Hammock Bruce D , Rabinovitch Marlene , Wu Joseph C , Nicolls Mark , Dejesus Perez Vinicio A
Published: April 2024

Background:
Pulmonary Arterial Hypertension (PAH) is a life-threatening disease characterized by loss of pulmonary microvessels and vascular remodeling. BMPR2 insufficiency in PAH is associated with oxidative stress and mitochondrial dysfunction but mechanism remain incompletely understood. We recently identified CES1 as a downstream target of BMPR2 and key mediator of EC survival. Carboxylesterase1 (CES1) is an endoplasmic reticulum(ER) enzyme responsible for lipid metabolism, cellular detoxification and redox balance. Here, we explore the consequences of CES1 deficiency and its link to EC dysfunction in PAH.

Hypothesis:
Loss of CES1 promotes EC dysfunction through oxidative stress and disruption of ER-mitochondrial homeostasis.

Methods:
PECs were transfected with siRNA/plasmid to knockdown/overexpress CES1. To induce oxidative stress, we used Luperox (100 μM). Chronic hypoxia (10% O
2
for 3 weeks) studies were carried out with male wild type and CRISPR-CES1 KO mice. Hemodynamic measurement and vessel morphometry was performed to assess right ventricular (RV) and vascular remodeling. Mitochondrial and ER structure and function was assessed by confocal microscopy and WB assays.

Results:
Both BMPR2 and CES1-deficient PECs have higher rates of apoptosis in the context of increased ROS production and mitochondrial fragmentation. Lipid staining with OilRedO demonstrated accumulation of lipid droplets in the cytoplasm of CES1-deficient PECs suggesting disruption in lipid metabolism. CES1-deficient PECs also showed an increase in ER stress markers (CHOP, BiP, IRE-1) compared to controls. Overexpression of CES1 was able to protect PECs against ROS accumulation and apoptosis while increasing tube formation in Matrigel assay. Compared to WT, CRISPR-CES1 KO mice demonstrated higher RV systolic pressures, RV and pulmonary microvessel remodeling in normoxia and with chronic hypoxia. Analysis of CES1-KO lung tissue demonstrates high lipid peroxidation, oxidative damage and reduced number of alveolar vessels.

Conclusions:
CES1 expression is crucial for PMVEC survival by preventing ROS and maintaining mitochondria/ER homeostasis. Therapeutic interventions to restore CES1 expression could serve as novel treatment approaches for PAH.
Abstract 14154: Genome-Wide Association Study of Dilated Cardiomyopathy in the VA Million Veteran Program
Authors: Aragam Krishna G , Charest Brian , Gaziano J M , Wilson Peter , Phillips Lawrence , Joseph Jacob , Sun Yan , Huffman Jennifer E ,   VA Million Veteran Program
Published: April 2024

Introduction:
Rare, Mendelian drivers of dilated cardiomyopathy (DCM) are well-established, but the contribution of common genetic variation to DCM risk has emerged more recently. As common variant discovery has largely relied on genome wide association studies (GWAS) of prospectively recruited DCM cases, we sought to conduct a GWAS of retrospectively-defined DCM from a large biobank.

Methods:
We used electronic health record-based phenotyping to define DCM in the VA Million Veteran Program (MVP), performed ancestry-specific GWAS in MVP participants of European and African genetic ancestry, and then conducted a trans-ethnic meta-analysis. We pursued replication of sentinel DCM single nucleotide polymorphisms (SNPs) in the UK Biobank. We further assessed the association of sentinel DCM SNPs with subclinical cardiac magnetic resonance imaging measures of left ventricular (LV) structure and function in UK Biobank, and with hypertrophic cardiomyopathy (HCM) in MVP.

Results:
Among 459,937 MVP study participants, mean age was 61.5, 43,971 (9.6%) were female, and 5,597 had DCM (N=3,786 European ancestry, N=1,811 African ancestry). In trans-ethnic meta-analysis, we identified eight genomic regions associated with DCM at genome-wide significance (P < 5x10
-8
). These included three of four known DCM associations near
HSPB7
,
LSM3
, and
BAG3
; and five novel genomic regions near
SLC39A8
,
CDKN1A
,
CD36
,
NEDD4L
, and
MAP3K7CL
. Three of the novel regions (at
CDKN1A
,
NEDD4L
, and
MAP3K7CL
) were replicated in UK Biobank (all p<8.0E-4; N=899 DCM cases, 449,574 controls). SNPs associated with increased DCM risk also associated with increased LV end-diastolic and end-systolic volumes and lower LV ejection fraction in UK Biobank participants without clinical heart failure or cardiomyopathy (N
>
31,614; all p < 0.01). Sentinel SNPs for DCM also showed a trend towards an opposite direction of association with HCM in MVP (N=1,533 HCM cases, 465,877 controls).

Conclusions:
We conducted the largest GWAS of DCM to date, and identified five novel, common genetic loci associated with DCM with replication of three novel loci in an external cohort. Our findings highlight the potential to leverage emerging biobank populations to scale common variant discovery for DCM.
Abstract 14177: Gender Disparities in Failure to Rescue After Cardiac Surgeries
Authors: Alabbadi Sundos , Rowe Georgina , Gill George , Chikwe Joanna , Egorova Natalia
Published: April 2024

Introduction:
Women have a higher risk of mortality than men after cardiac surgery, independent of other risk factors. Death after postoperative complications, known as “failure to rescue (FTR)”, is a nationally endorsed quality care metric. This study was designed to evaluate differences in FTR after cardiac surgery in women and men.

Methods:
In this retrospective analysis, post-operative outcomes of 30,973 men (70.4%) and 13,033 women (29.6%) aged over 18 years undergoing coronary bypass or valve surgery identified from statewide administrative data from New York (2016-2019) and California (2016-2018) who experienced at least one serious postoperative complication, were compared according to gender. The primary outcome was FTR. Multivariable logistic regression was used to identify independent predictors of death after complication. Propensity matching was used to adjust for baseline differences between genders and yielded 12,608 pairs.

Results:
Women were older (mean age 67.8 vs 66.6, P<0.001), more frail (median frailty score 0.1 vs 0.07, P<0.001) and had more comorbidities (median Charlson score 2.5 vs 2.3, p<0.001) than men. The overall FTR rate was 5.7% (2,524 of 44,006). Men were less likely to die after a complication than women (4.8% vs 8%, P<0.001). Independent predictors of FTR included female gender, age≥75 years, higher Charlson comorbidity score, and higher number of postoperative complications (Figure). In the propensity matched cohort, FTR was significantly lower among men than women (5.7% vs 7.9%, P<0.001). This difference in FTR was mainly driven by the difference in FTR after respiratory failure, bleeding, myocardial infarction, shock, and acute kidney failure.

Conclusion:
Women are more likely to die following complications after cardiac surgery, independent of clinical and socioeconomic characteristics, than men. Clinical practices contributing to this disparity may be an appropriate target for quality improvement.
Abstract 14260: Suppression and Replacement Gene Therapy for Type 2 Long QT Syndrome
Authors: Bains Sahej , Dotzler Steven , Zhou Wei , Kim CS John , Tester David J , Ackerman Michael J
Published: April 2024

Introduction:
Type 2 long QT syndrome (LQT2) is caused by loss-of-function variants in the
KCNH2
-encoded K
v
11.1 potassium channel which is essential for the rapid delayed rectifier channel (I
Kr
) that governs phase 3 of cardiac action potential (AP). No current therapies target the molecular cause of LQT2.

Methods:
A dual-component “suppression-and-replacement” (SupRep)
KCNH2
gene therapy was created by cloning into a single construct a custom-designed
KCNH2
shRNA that produces ~80% knockdown (suppression) and a “shRNA-immune” (shIMM)
KCNH2
cDNA modified by the introduction of synonymous single nucleotide substitutions within the shRNA target site (replacement). The ability of KCNH2-SupRep gene therapy to suppress and replace LQT2-causative variants in
KCNH2
was evaluated via heterologous expression in TSA201 cells. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated from two patients with LQT2 (KCNH2-G604S and -N633S). CRISPR-Cas9 corrected isogenic control iPSC-CMs were made. Both lines were treated with KCNH2-SupRep or non-targeting control shRNA (shCT). FluoVolt voltage dye was used to measure the APD.

Results:
KCNH2-SupRep achieved mutation-independent suppression of wild-type
KCNH2
and both LQT2-causative variants with simultaneous replacement of KCNH2-shIMM as measured by allele-specific qRT-PCR. Treatment with KCNH2-SupRep resulted in shortening of the pathologically prolonged APD at 90% repolarization (APD
90
) to near isogenic control APD
90
levels (G604S: isogenic controls, 424
+
39 ms and N633S: isogenic controls, 433
+
16 ms) compared to treatment with non-targeting shCT (G604S: SupRep treated, 399±105 ms vs. shCT treated, 577±39 ms, p<0.0001; N633S: SupRep treated, 432±85 ms vs. shCT treated, 483±65 ms, p<0.005).

Conclusions:
We provide the first proof-of-principle gene therapy for correction of LQT2. Like our sentinel discovery of SupRep gene therapy for LQT1, KCNH2-SupRep successfully suppressed and replaced
KCNH2
to normal wild-type levels. In TSA201 cells, co-transfection of LQT2 variants and KCNH2-SupRep caused mutation-independent suppression-and-replacement of
KCNH2
. In LQT2 iPSC-CMs, KCNH2-SupRep shortened the APD, thereby eliminating the pathognomonic feature of LQT2.
Abstract 14265: The Role Of Vesicle-incorporated Long Noncoding RNA H19 In Cardiovascular Disease
Authors: Maus Katharina , Hosen Rabiul , Jansen Feilx
Published: April 2024

Background:
Recent studies have demonstrated that pathogenesis of cardiovascular disease (CVD) includes higher levels of circulating extracellular vesicles (EVs). Those EVs can contain different types of cargoes including long noncoding RNAs (LncRNAs). Here we aim to elucidate the cellular function and mechanism of action of LncRNA H19 with particular interest in EV-mediated intercellular communication.

Methods and Results:
Loss of function of H19 was performed
in vitro
using RNA interference in vascular endothelial cells (ECs). After H19 loss of function, various assays were conducted to assess specific cellular properties and functions in both EV-donor and recipient cells. The cellular properties in terms of viability and apoptosis as well as the cellular functions regarding migration, proliferation, and angiogenesis were impaired in EV-donor cells. Intriguingly, both cellular properties and functions were improved in EV-recipient cells. Since our results indicated that the angiogenic sprouting was impaired in cells after knockdown of H19, we want to perform angiogenesis array to identify dysregulated genes that are involved in angiogenesis. To unravel the molecular mechanism of H19 further, we sought to identify binding partners of H19 to unveil how vesicle-incorporated H19 exerts it specific functions in CVDs and cardiovascular cells
in vitro
.

Conclusion:
Our data suggests that vesicular transport of H19 regulates the cellular properties and function of target ECs. Further investigation is required to identify specific H19 molecular mechanism of action that plays a crucial role in cardiovascular cells and disease.

Figure 1: Schematic representation of EV-mediated intercellular transfer of lncRNA H19.
LncRNA H19 can be transferred to the target cell via extracellular vesicles (EVs). Studies showed that H19 can exploit different regulatory functions endothelial cells.
Abstract 14336: Association of Mid-Life Cardiovascular Disease and Late-Life Alzheimer's Disease Pathology: Insights From Heart Score Study
Authors: Saeed Anum , Chang, Yue-Fang , Lopez Oscar L , Reis Steven , Cohen Ann D
Published: April 2024

Introduction:
Data show an association of CVD risk factors in mid-life with older age dementia. Atherosclerosis (ATH) and arteriosclerosis (ART) are both implicated in incident dementia however their relationship with incident Alzheimer’s disease (AD) remains elusive. We investigated the association of mid-life cardiovascular risk factors and mid-life subclinical CVD (ATH and ART) with late-life AD pathology.

Methods:
Non-demented participants over the age of 65 from the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study underwent brain PET acquisition (2018-2020) for AD specific amyloid deposition [by Pittsburgh Compound B (PiB)]. Pearson’s correlation and OR (95% CI) using Cox regression for association of cortical PiB retention with mid-life (2003-2005) markers of ATH (coronary artery calcium [CAC] score and carotid intima thickness [CIMT]) and ART (vascular stiffness) were calculated.

Results:
Among 121 participants in late-life (mean age ~79y), age was significantly correlated to lower cognition (
r
=0.19, p=0.03) but gender, race and diabetes were not. Late-life AD pathology was not significantly associated with mid-life CAC (>150) [OR=0.12 (0.01, 2.36); p=0.16] or CIMT [OR=1.80 (0.84, 3.86); p=0.40]. Presence of increased vascular stiffness in mid-life showed a significant association with late-life PiB retention
(Table
).

Conclusions:
In a small number of biracial middle-aged adults, subclinical markers of atherosclerosis did not independently predict increased biomarkers of AD pathology. However, vascular stiffness in mid-life was significantly associated with late-life brain biomarkers of Alzheimer’s disease pathology. Further research can elucidate the role of mid-life athero- and arteriosclerosis in Alzheimer's disease dementia.
Abstract 14355: Metabolic Dysregulation and Incident Atrial Fibrillation in Older Adults
Authors: Pellegrini Cara N , Buzkova Petra , Oesterle Adam , IX Joachim H , Siscovick David S , Heckbert Susan R , Tracy Russell , Hirsch Calvin , Mukamal Ken J , Djousse Luc , Kizer Jorge R
Published: April 2024

Introduction:
Obesity and dysmetabolism are major risk factors for atrial fibrillation (AF). Fasting and post-load levels of glucose and non-esterified fatty acids (NEFA) reflect different facets of metabolic regulation, but their contributions to AF risk have not been studied simultaneously in prior studies. We assessed fasting and post-load glucose and NEFA in an older cohort to identify their independent associations with new-onset AF, and secondarily with baseline ECG parameters known to be markers of AF risk.

Methods:
This study focused on participants from the community-based Cardiovascular Health Study who were free of prevalent AF and had serum collected in the fasting state and after an oral glucose tolerance test. Maximal p wave duration and p wave terminal force in V1 (PTFV1) were measured from 12-lead ECG. Associations were evaluated with linear regression for ECG parameters, and Cox regression for AF.

Results:
The study included 1,877 participants (age 77.7±4.4). After adjustment, both fasting and post-load glucose, but not NEFA, were positively associated with higher PTFV1. When fasting and post-load glucose were entered together, only the relationship for the latter remained significant (63 μV*ms greater PTFV1 per SD increment in post-load glucose [p=0.028]). During median follow-up of 11.4 years, 717 cases of incident AF occurred. Post-load glucose, but not fasting glucose or either NEFA measure, showed an association with incident AF (adj. HR per SD=1.11 [95% CI=1.02, 1.21], p=0.017). There was significant interaction by sex (p=0.015). The positive relationship of post-load glucose with AF was observed in women (adj. HR per SD=1.21 [1.09, 1.35], p<0.001), but not men (adj. HR per SD=0.97 [0.85, 1.12], p=0.714).

Conclusions:
Among older adults, post-load glucose, but not fasting glucose or NEFA measures, was positively associated with incident AF, with consistent findings for PTFV1 on baseline ECG. The relationship with AF appeared specific to women. Because post-load glucose is a marker of both pancreatic β-cell insufficiency and skeletal muscle decline, these findings suggest that interventions to address such tissue-organ dysfunction in older women might prevent AF in this high-risk population.
Abstract 14367: Elevated Creatinine Levels Are Associated With Vascular Dysfunction in Liver Transplant Recipients
Authors: Chavez Domenico A , Carper Moriah C , Bohmke Natalie J , Martin Linsey , Bhati Chandra , Wolver Susan , Siddiqui Mohammad S , Kirkman Danielle L
Published: April 2024

Introduction:
Liver transplant (LT) recipients have an increased risk of developing cardiovascular disease (CVD) after transplant. The physiological mechanisms driving LT-related CVD are not fully understood. Renal impairment post-transplant may contribute to CVD risk in LT recipients. The aim of this study was to investigate the relationship between plasma creatinine levels and vascular function in LT patients.

Methods:
Conduit artery endothelial function was measured via flow-mediated dilation of the brachial artery (FMD
BA
) with duplex ultrasound in 13 LT patients (7 Male, 6 Female; Median [IQR]: Age 59 [56 - 64] years). Parameters of carotid artery function (distension, distensibility, compliance and stiffness) were assessed using B mode ultrasound and central aortic pressure waves that were synthesized from radial artery waveforms acquired by applanation tonometry in 13 LT patients (6 Male, 7 Female; Age 57 [56 - 64] years). Blood samples were analyzed for plasma creatinine by nuclear magnetic resonance spectroscopy.

Results:
Conduit artery endothelial function via FMD
BA
(4.07 [3.52 - 6.40] %) was negatively associated with plasma creatinine levels (1.30 [1.08 - 1.56] mg/dL;
r
= -0.63,
p
= 0.03). Plasma creatinine levels were also inversely associated with carotid artery distension (0.53 [0.35 - 0.61] mm,
r
= -0.74,
p
= 0.006), distensibility (25.62 [20.65 - 33.03] 10
-3
·kPa
-1
,
r
= -0.59,
p
= 0.04), and compliance (1.19 [0.82 - 1.41] 10
-6
·m
2
·kPa
-1
,
r
= -0.66,
p
= 0.02), and positively associated with carotid stiffness (6.07 [5.35 - 6.76] m·s
-1
,
r
= 0.59,
p
= 0.04) as shown in Figure 1.

Conclusions:
Our results indicate that LT patients with higher levels of creatinine have impaired conduit artery endothelial function and compromised carotid artery function, making these individuals more susceptible to the development of atherosclerosis and stroke. The presence of renal dysfunction after LT may contribute to CVD risk and warrants investigation in future trials.
Abstract 14396: Cardioprotective Effects Of Glycyrrhizin On Hyperglycemic Cardiac Tissues
Authors: Chattopadhyay Munmun , Thakur Vikram , Joddar Binata
Published: April 2024

Introduction:
Myocardial fibrosis and dysfunction is one of the major cardiac complications of long-term diabetes. Prolonged hyperglycemia is known to induce myocardial dysfunction often leading up to heart failure.

Hypothesis:
The objective of this study was to investigate the cardioprotective effect of glycyrrhizin (GLC) on myocardial damage in engineered in-vitro human cardiac tissues. Engineered 3D tissue chips present an ideal microenvironment via therapeutically relevant interfaces to study molecular- and cellular-level events and mimic human-specific disease states, and identify new therapeutic targets in vitro.

Methods:
AC16 human cardiomyocyte cells were used to 3D bioprint cardiac tissue chips based on prior published work. In our study, the 3D bioprinted cardiac tissue chips (CTC) were cultured using normo- (5mM) and hyper-glycemic (25mM) conditions for up to 48 hrs. For the GLC treatment group, a subset of CTC cultured using hyperglycemic conditions were treated with 50 mM of GLC for 24 hours.

Results:
CTC cultured under hyperglycemic conditions demonstrated altered levels of connexin-43 (CX43) and Troponin-I implying cardiomyocyte injury. Exposure to hyperglycemia revealed changes in epigenetic markers: histone methylation marker (H3K9me)-1, Sirtuin-1, and Histone Deacetylase (HDAC)-2 as well as in inflammatory and stress related mediators such as heat shock protein (HSP)-60, receptor for advanced glycation end products (RAGE), toll like receptor (TLR)-4, high mobility group box (HMGB)-1 and CXC chemokine receptor (CXCR)-4. CTC exposed to 25mM glucose for 24 hours resulted in the downregulation of HSP60 and Sirtuin-1. Prolonged exposure to hyperglycemia led to decrease in the expression of CX43 and CXCR4; thereby adversely affecting cardiomyocyte function. Upregulated expression of DNA-binding nuclear protein HMGB1 along with changes in H3K9me1 indicated long-term hyperglycemia-induced damage to cardiomyocytes. GLC treated CTC exhibited a decrease in the expression of RAGE, TLR4 and also demonstrated altered expression of CX43, CXCR4, and troponin I.

Conclusions:
This study suggests that GLC possesses cardioprotective effects in human cardiomyocytes exposed to prolonged hyperglycemia.
Abstract 14409: Elucidating Clinical Phenotypes of Patients With Mixed Shock Admitted to Cardiac Intensive Care Units: Insights From the Critical Care Cardiology Trials Network
Authors: Dewanjee Aditya , Kochar Ajar , Berg David D , Bohula Erin A , Park Jeong-Gun , Van Diepen Sean , Katz Jason N , Morrow David A , Sinha Shashank S
Published: April 2024

Background:
Emerging data suggests that patient with mixed cardiogenic and vasodilatory shock have high morbidity and mortality; however, this population is still poorly understood and is not well-characterized.

Methods:
The Critical Care Cardiology Trials Network is a multicenter network of advanced cardiac intensive care units (CICUs) in North America coordinated by the TIMI Study Group. Each CICU contributed an annual 2-month period of all consecutive medical CICU admissions from 2017-2020 (n=13,300). Mixed shock (MS) subjects were stratified into those with acute MI (AMI-MS) and those without (non-AMI-MS).

Results:
Among 3884 CICU admissions with shock, 840 (22%) presented with MS; 169 AMI-MS and 671 non-AMI-MS. Mean age was 66y, 37.1% were female, and 69.5% were white. Median Sequential Organ Failure Assessment was 10.0 (25
th
-75
th
%ile, 7.0-12.5). On presentation, AMI-MS had more end-organ injury: lactate (3.5 vs. 2.7,
p
< 0.01) & AST (126 vs. 54,
p
< 0.01). AMI-MS had fewer CV & non-CV comorbidities (
p
< 0.01 for all). Sepsis was less common in AMI-MS (47.8% vs. 67.6%,
p
< 0.0001). Use of advanced ICU therapies was high, as 25.4% overall cohort required renal replacement therapy (RRT). AMI-MS required more mechanical ventilation (81.1% vs. 67.5%,
p
< 0.001), invasive cardiac procedures (76.3% vs. 16.2%,
p
< 0.0001), and temporary mechanical support (tMCS) (56.8% vs. 16.7%, p < 0.0001). Both AMI-MS and non-AMI-MS patients had high in-hospital mortality (50.3% [95% CI 42.5% - 58.1%] & 43.5% [95% CI 39.7% - 47.4%], respectively). AMI-MS patients with a worst pH < 7.25, ≥ 3 pressors, and RRT use have a 4.9-fold, 3.9-fold, and 2.9-fold risk of in-hospital mortality, respectively (Figure).

Conclusion:
In a contemporary multicenter analysis of advanced CICUs, patients with mixed shock have high in-hospital mortality and frequent need for advanced ICU therapies. Patients with AMI-MS present with particularly high shock severity and subsequent resource utilization.
Abstract 6983: Real-World Evaluation of In-Hospital Mortality and Vascular Complications in Patients Receiving Impella Support in a Community Based Health Care System
Authors: Kalyan Sundaram Arvind , Crissinger Samantha , Vanenkevort Erin , Kandadai Sreelakshmi , Voyce Stephen J
Published: April 2024

Introduction:
Impella is a peripherally inserted ventricular assist device used for hemodynamic support in patients during high risk percutaneous coronary interventions (PCI) and for management of cardiogenic shock. The aim of our study is to identify the mortality and vascular complications related to Impella placement in a real-world community health care setting.

Methods:
This is a retrospective observational study of patients who had Impella device implanted for high risk PCI and/or cardiogenic shock at three hospitals in the Geisinger Health Care System from January 2015-March 2020.

Results:
Ninety-nine patients had devices implanted during this time. One patient was excluded from analysis due to missing data. In hospital mortality rate was 31.6% for the entire group. The mortality rates varied significantly based on the acuity of procedure (p = <.001). In-hospital mortality rates for patients receiving the Impella electively, urgently, emergently, and as a salvage procedure, was 0, 17.1, 46.4 and 65% respectively. The overall rate of vascular complications was 13.1% and was not related to the acuity of procedure (p = .16). Patients with a greater body mass index (BMI) had an increased frequency of vascular complications (OR = 1.89 95%CI: 1.31, 2.47, p < .0001). Although not significantly significant, 14.7% of males had vascular complications compared to 9.7 % of females (p = .49).

Conclusions:
In-hospital mortality rates of patients with Impella implantation varies significantly based on the acuity of the procedure. Mortality remains high in patients with emergent & salvage procedures. 2. Patients with higher BMI develop more frequent vascular complications. 3. No statistically significant difference in gender related vascular complication rates was found.
Abstract 8879: Circulating Levels of MicroRNA-122 and Hepatic Fat Changes in Response to Lifestyle Intervention: Central Magnetic Resonance Imaging Randomized Controlled Trial
Authors: Xue Qiaochu , Wang Mengying , Li Xiang , Krohn Knut , Ziesche Stefanie , Ceglarek Uta , Bluher Matthias , Keller Maria , Yaskolka Meir Anat Y , Heianza Yoriko , Kovacs Peter , Shai Iris , Qi Lu
Published: April 2024

Introduction:
Compelling evidence has linked liver-specific microRNA-122 (miR-122) expression with hepatic fat distribution; however, little is known about the relations between changes in circulating miR-122 and liver fat in response to weight-loss interventions. We aimed to prospectively investigate the association between serum miR-122 and changes of hepatic fat content during 18-month diet and physical activity interventions.

Methods:
The CENTRAL trial is an 18-month randomized controlled trial among adults with abdominal obesity or dyslipidemia. Subjects were randomly assigned to a low-fat (LF) diet or a Mediterranean/low-carbohydrate (MED/LC) diet. After six months of dietary intervention, each diet group was further randomized into added physical activity groups (LFPA+, MED/LCPA+) or no added physical activity groups (LFPA-, MED/LCPA-) for the following 12 months of intervention. The current study included 220 participants with repeated measurements on serum miR-122 and hepatic fat content (percentage) over 18 months.

Results:
In the study participants, serum concentration of miR-122 significantly increased from baseline to 18 months, while no difference was observed across the four intervention groups. We found a significant association between miR-122 and hepatic fat percentage at baseline, as per unit increment in log-transformed miR-122 was associated with 3.79 higher hepatic fat content (
P
trend<0.001). In addition, we found that a higher elevation in log-transformed miR-122 was associated with a greater reduction in hepatic fat percentage during 18-month interventions, independent of weight loss (β=1.56,
P
trend=0.002). We also found a significant interaction between changes in miR-122 and baseline fasting plasma glucose with hepatic fat content changes in 18 months (
P
interaction=0.02). The association between changes in miR-122 and hepatic fat content changes appeared to be stronger among participants with higher baseline fasting glucose levels than those with lower levels.

Conclusion:
Our data indicate that participants with higher serum miR-122 levels may benefit more in reduction of hepatic fat content in response to Mediterranean/low-carbohydrate diet and physical activity interventions.
Abstract 8899: DOAC Use for Stroke Prevention in Patients with Atrial Fibrillation and Elevated Body Mass Index
Authors: Foglesong Adam , Armstrong Justin , Mando Ramy , Halalau Alexandra
Published: April 2024

Background:
The incidence of comorbid obesity and atrial fibrillation (AF) has been increasing. Direct Oral Anticoagulants (DOACs) have become the first-line agents for cerebrovascular accident (CVA) prophylaxis in patients with AF due to their superior efficacy and lower bleeding risk when compared to coumadin. The incidence of acute ischemic CVA while on a DOAC in the non-obese population is 1.2%. Evidence on the efficacy of DOACs in preventing AF related CVAs in the obese population is limited.

Methods:
Electronic medical records from 8 hospitals within the same health system were queried. Patients age
>
18 years with a BMI
>
40 kg/mm
2
and AF on a DOAC (Rivaroxaban, Apixaban, or Dabigatran) were included in our study. Individual charts from 2010 to 2020 were reviewed for neuroimaging (computed tomography and MRI) following the start date of a DOAC confirming the presence or absence of an acute hemorrhagic or ischemic CVA.

Results:
We included 1935 patients in the study. Acute ischemic CVA was noted in 17 patients (0.9%) by head CT (11/17 confirmed by MRI). Hemorrhagic CVA was noted in one patient (0.1%) by head CT. 155 (8%) had a head CT without evidence of CVA, of which, 5 (3.2 %) had evidence of an acute ischemic CVA by MRI. Therefore, 22 patients (1.1%) had evidence of acute ischemic CVA on neuroimaging. The remainder of patients (N = 1762, 91.1%) did not have indications for neuroimaging and were considered to have successful CVA prophylaxis. In total, 1912 (98.8%) of patients with a BMI
>
40 treated with a DOAC for AF did not demonstrate neuroimaging evidence of CVA.

Conclusions:
Although we expected to find higher CVA rates due to ineffective anticoagulation in the obese population, DOACs appear to be an effective therapy for CVA prophylaxis in obese patients with AF. The incidence of acute ischemic CVA in the obese population while on a DOAC is comparable to the non-obese population. Further prospective studies are needed to confirm the findings of this analysis.