bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13076: A Rare Stopgain Variant in
SLC25A2
Associates With Low Nitric Oxide and Poor Clinical Outcome in Hypoplastic Left Heart Syndrome
Authors: Zhu Wenjuan , Xu Xinxiu , Lin Jiuann-huey I , Adams Phillip S , Lo Cecilia W
Published: June 2023

Introduction:
Mitochondrial respiration defects accompanied by low nitric oxide (NO) are associated with heart failure in congenital heart disease (CHD) patients with hypoplastic left heart syndrome (HLHS). Here we investigated the genetic etiology of low NO in patients with CHD.

Hypothesis:
Mutations in mitochondrial-related genes involved in NO metabolism contributes to the low NO associated risk for heart failure and need for heart transplantation in HLHS.

Methods and Results:
We performed a case-control association study among 588 white CHD cases including 41 with HLHS, and 24,143 white controls from the genome aggregation database (gnomAD). A rare conserved stopgain variant (rs562886845) in
SLC25A2
encoding mitochondrial ornithine transporter was significantly enriched among the HLHS patients with poor clinical outcome (Group II, Table 1), with 15.8% carrying this mutation, yielding odds ratio of 17.07 (
p
= 5.23 х 10
-4
) in comparison to CHD patients without left ventricular outflow tract obstruction or 7.63 (
p
=2.68 х 10
–3
) in comparison to gnomAD control cohort. Significantly,
SLC25A2
is the only mitochondrial transporter exporting asymmetric dimethylarginine, a natural NO synthase inhibitor. The three HLHS patients with this
SLC25A2
variant showed very low nasal NO (nNO), a proxy for endogenous NO production capacity. All three patients had received heart transplant, with two being heterozygous and one homozygous for this variant. Significantly, the HLHS patient with the homozygous mutation had nNO at background levels (2.8 nl/min at 7 years of age as compared to >200 nl/min expected nNO).

Conclusions:
Our findings uncovered an essential role for
SLC25A2
in determining NO production capacity in patients with HLHS. As all three HLHS patients with this variant and very low nNO survived with heart transplant, this variant should be further investigated as a genetic marker for predicting the need for early heart transplant in HLHS.
Abstract 13083: Lipoprotein(a) is a Residual Cardiovascular Risk Factor in Statin Treated Stroke Survivors - Insights From the SPARCL Trial
Authors: Chemello Kevin , Gallo Antonio , Lambert Gilles
Published: June 2023

Introduction:
Elevated lipoprotein (a) [Lp(a)] plasma levels are causally associated with CAD. The association between Lp(a) and stroke is however less clear. The SPARCL trial has demonstrated the superiority of 80mg atorvastatin to placebo for the prevention of stroke in patients with recent stroke or TIA. The aim of the current study was to investigate if Lp(a) is predictive of recurrent cerebrovascular and incident coronary events in these patients.

Methods:
Lp(a) concentration and apolipoprotein(a) [apo(a)] isoform size, a strong determinant of Lp(a) plasma levels, were measured by LC-HRMS in samples collected at baseline from 2814 SPARCL participants (1418 randomized to atorvastatin & 1396 to placebo). Within each treatment arm, we compared patients in the highest quartile (
>84.0nmol/L
) with those in the lowest quartiles of Lp(a) concentrations and patients in the lowest quartile (
<25.9 KIV domains
) with those in the highest quartiles of apo(a) size distributions. The relationship between these parameters and subsequent events was established with a Cox proportional hazard model adjusted for age, sex, type of entry event, time since entry event, BMI, smoking, hypertension, non HDLC and DM.

Results:
In patients randomized to atorvastatin, elevated Lp(a) concentrations and shorter apo(a) isoforms were independently associated with an increased risk of coronary events [HR (95% CI) of 1.607 (1.007-2.563)
p=0.047
& 2.052 (1.303-3.232)
p=0.002
, respectively]. These associations were primarily driven by a significantly higher incidence of coronary revascularisation procedures, stable angina requiring hospitalization, and MI. No such association was found in patients randomized to placebo [0.925 (0.606-1.412) & 1.105 (0.735-1.659)]. We did not observe any significant association between elevated Lp(a) concentrations or short apo(a) isoforms and the risk of recurrent cerebrovascular events in patients randomized to atorvastatin [0.794 (0.586-1.076) & 1.114 (0.760-1.352)] or placebo [0.914 (0.688-1.214) & 0.940 (0.709-1.248)].

Conclusion:
Lp(a) contributes to the residual CAD risk of statin-treated stroke/TIA survivors, paving the way for the use of novel therapies targeting Lp(a) in patients with a history of stroke and elevated Lp(a).
Abstract 13103: Defective Vascular Smooth Muscle Cell Tafazzin Impairs Mitochondrial Function and Promotes Atherosclerosis
Authors: Dong Cindy , Finigan Alison , Figg Nichola , Bennett Martin , Yu Emma
Published: June 2023

Introduction:
Tafazzin acylates immature monolysocardiolipin to form mature cardiolipin. Cardiolipin is the signature phospholipid of the mitochondrial inner membrane required for respiratory efficiency and regulation of apoptosis. Mitochondrial respiration is reduced in atherosclerosis. However, whether tafazzin regulates vascular smooth mucle cell (VSMC) mitochondrial function and contributes to atherosclerosis is unclear.

Hypothesis:
Tafazzin regulates VSMC mitochondrial function and atherosclerosis development.

Methods:
We examined tafazzin expression and regulation in human plaques and VSMCs. We determined the in vitro effects of tafazzin using siRNA mediated cell silencing or lentiviral infection to express either tafazzin (Taz) or tafazzin with a transacylase defective mutation (Taz
H69Q
). We also generated mice expressing VSMC restricted Taz or Taz
H69Q
and crossed them with apolipoprotein E deficient mice (SM22α-Taz/ApoE
-/-
or SM22α-Taz
H69Q
/ApoE
-/-
) to study tafazzin in vivo

Results:
Tafazzin mRNA and protein is decreased in plaque and plaque VSMCs. MicroRNA 125a-5p expression is increased in plaques, downregulates tafazzin expression and is induced by oxidised low density lipoprotein. Tafazzin silencing and expression of Taz
H69Q
reduces mitochondrial respiration, decreases ATP content (0.13±0.01nmoles vs 0.21±0.01nmole, n=4), and promotes apoptosis. SM22α-Taz
H69Q
/ApoE
-/-
mice showed increased plaque burden (28±2.3% vs 17±2.1%, n=17), increased necrotic core and reduced fibrous cap areas. In contrast, over-expression of tafazzin increases VSMC mitochondrial respiration and protects against apoptosis. SM22α-Taz/ApoE
-/-
mice showed no change in plaque burden but increased features of plaque stability. SS-31, which binds and stabilises cardiolipin, improves mitochondrial respiration and decreases apoptosis in SM22α-Taz
H69Q
/ApoE
-/-
VSMCs.

Conclusions:
Tafazzin expression is decreased in plaque VSMCs and is negatively regulated by microRNA 125a-5p. Defective tafazzin decreases mitochondrial respiration, increases apoptosis and promotes atherosclerosis. Tafazzin is therefore an important and unrecognised regulator of VSMC mitochondrial function and atherosclerosis.
Abstract 13113: Health-Related Quality of Life After Neonatal Treatment of Symptomatic Tetralogy of Fallot: Insights From the Congenital Cardiac Research Collaborative
Authors: Zampi Jeffrey D , Nicholson George T , Goldstein Bryan H , Glatz Andrew C , Petit Christopher J , McCracken Courtney E , Qureshi Athar M , Goldberg Caren S , Romano Jennifer C , Law Mark A , Meadows Jeffery J , Shahanavaz Shabana , Batlivala Sarosh P , Maskatia Shiraz A , Pettus Joelle A , Beshish Asaad , Stack Kathryn O , Khan Hala Q , Parekh Shalin , Ilardi Dawn L
Published: June 2023

Introduction:
Health-related quality of life (HRQOL) is impaired for patients with chronic illnesses and critical congenital heart disease (cCHD). For symptomatic neonates with tetralogy of Fallot who require neonatal intervention (sTOF), existing studies are limited but suggest early surgical management and ongoing disease burden negatively impact HRQOL. The current study aims to explore HRQOL in sTOF patients after primary repair (PR) vs. staged repair (SR; initial palliation with subsequent complete repair).

Methods:
The Pediatric Quality of Life Inventory (PedsQL) was used to assess HRQOL. Age-appropriate PedsQL modules and a parent survey were sent to all living sTOF patients with neonatal intervention from 2005-2017 across 9 centers. These were compared to established population data from children who are healthy, have chronic illness, and have cCHD. Differences in patient and clinical factors were compared between those with normal and low (>2 standard deviations below the mean) HRQOL scores.

Results:
Of 511 surveys sent, 143 were returned (28%). Of the respondents (53% male, age 3.2-15.9 years), PedsQL scores were lower than the healthy population (total score 75 vs 84, p<0.001) but similar to patients with chronic illnesses (74, p=0.64) and cCHD (76, p=0.72). Although only 7% and 2% of parents rated their child’s overall health and QOL as fair or poor, up to 27% of patients had PedsQL scores >2 SD below the healthy population mean. Factors associated with low HRQOL included longer duration of inhalational anesthetic exposure within 18 months of life (p=0.04) and any hospital complications after index procedure (p=0.01). There was no association between HRQOL and initial treatment strategy (PR vs SR, p=0.9).

Conclusions:
Lower HRQOL in sTOF is consistent with those with chronic illnesses and other forms of severe CHD. Initial treatment strategy was not associated with differences in HRQOL in sTOF patients so future comparison to other CHD groups, including non-cyanotic TOF patients, may help elucidate drivers of lower HRQOL. The discrepancy between parental description of QOL and standardized measurement of QOL is striking, warranting further investigation of parental expectations and potential impact on health resource utilization.
Abstract 13114: Micro RNA206 Secreted From Growing Skeletal Muscle Promotes Angiogenic Response in Endothelial Cells
Authors: Hayashi Hiroya , Izumiya Yasuhiro , Ishida Toshifumi , Arima Yuichiro , Hayashi Ou , Tsujita Kenichi , Fukuda Daiju
Published: June 2023

Introduction:
In addition to aerobic exercise, it has been recognized that resistance exercise has beneficial effects for the patients with peripheral arterial disease. Recently, muscle-derived exosomes are demonstrated to convey many types of signaling molecules including microRNAs (miRNAs).

Hypothesis:
We assessed the hypothesis that exosomal miRNA secreted by growing muscle promotes angiogenic response in endothelial cells.

Methods:
We utilized skeletal muscle-specific inducible Akt1 transgenic (Akt1-TG) mice that can induce growth of skeletal muscles without exercise training. Exosomes was purified combined usage of ultracentrifugation, and miRNAs were extracted from purified exosomes by spin column-based method. Real-time PCR array and droplet digital PCR was performed to evaluate exosomal miRNA expression.

Results:
Akt1-TG mice showed remarkable skeletal muscle growth 2 weeks after gene activation (weight of gastrocnemius muscle: 0.21±0.03 vs 0.16±0.02, g, p<0.01). The amount of exosomal proteins did not different between Akt1-TG mice and WT mice (977.7±11.3 vs 826.0±45.2, μg/mL serum, p=0.07). KEGG pathway frequency analysis for 4665 target genes identified by real-time PCR array of miRNAs revealed a significant increase in Akt and its downstream signaling pathways. Among upregulated miRNAs, droplet digital PCR identified that miR-1, -133 and -206 expression was significantly upregulated in Akt1 TG mice compared with WT mice in serum. miR206 was increased in IGF-1-stimulated myotubes. PKH26-labeled exosomes were taken up by human umbilical vein endothelial cells. Exogenous supplementation of exosomal miRNA206 promoted angiogenesis as revealed by spheroid assay, and increased expression of HIF-1 and VEGF in endometrial cells.

Conclusions:
Exosomal miR206 was upregulated in blood stream in Akt1-TG mice and IGF-stimulated cultured myotubes. Exogenous supplementation of miR206 promoted angiogenic response in endothelial cells. Our data suggest that miR206 secreted from growing muscle act on endothelial cells and promote angiogenesis.
Abstract 13123: Sex-Specific Associations Between Hypertension in the Early Forties and Arterial Stiffness 27 Years Later: The Hordaland Health Study
Authors: Kringeland Ester , Midtbo Helga , Gerdts Eva
Published: June 2023

Background:
Hypertension is associated with arterial stiffening. Less is known about sex-specific associations of hypertension in the early forties with increased arterial stiffness later in life.

Methods:
BP was measured in 1121 women and 932 men at mean age 42 years (baseline). Participants were grouped into normotension (BP<130/80 mmHg), stage 1 hypertension (BP 130-139/80-89 mmHg) and stage 2 hypertension (BP≥140/90 mmHg). Arterial stiffness was measured by pulse wave velocity (PWV) after 27 years follow-up. Increased arterial stiffness was defined as PWV>10m/s in both sexes. Associations between baseline BP categories and increased arterial stiffness were tested in logistic regression analyses and presented as odds ratios (OR) and 95% confidence intervals (CI).

Results:
At baseline, a larger proportion of men than women had stage 1 and stage 2 hypertension (330 men (35%) and 266 women (24%) with stage 1 and 241 men (26%) and 105 women (9%) with stage 2 hypertension, p<0.001 for sex difference). At follow-up, 289 men (31%) and 197 women (18%) had increased arterial stiffness (p<0.01). In univariable analysis in women, stage 1 (OR 2.44, 95 % CI 1.72-3.47) and stage 2 hypertension (OR 3.34, 95% CI 2.10-5.31) were associated with increased arterial stiffness. After adjustments for baseline body mass index, smoking, heart rate, serum cholesterol and education, stage 1 (OR 2.19, 95% CI 1.52-3.15) and stage 2 hypertension (OR 2.74, 95% CI 1.67-4.48) remained associated with increased arterial stiffness in women. In univariable analyses in men, stage 1 (OR 1.55, 95% CI 1.11-2.16) and stage 2 hypertension (OR 1.88, 95% CI 1.32-2.68) were associated with increased arterial stiffness. After similar multivariable adjustments, these associations became non-significant in men (OR 1.34, 95% CI 0.95-1.89 for stage 1 and OR 1.40, 95% CI 0.95-2.06 for stage 2 hypertension, respectively). This sex difference was confirmed by a significant test for interaction (p=0.03).

Conclusion:
In the Hordaland Health Study, having stage 1 and stage 2 hypertension in the early forties predicted increased arterial stiffness in women, but not in men.
Abstract 13129: Human
in vitro
Study on Pulsed Electric Field Cardiac Ablation Cell Sensitivity
Authors: Casciola Maura , Feaster TK , Vadlamani Ram Anand , Keck Devin , Davalos Rafael V , Blinova Ksenia
Published: June 2023

Introduction:
Catheter cardiac ablation is a standard treatment for atrial fibrillation for patients that do not respond to drugs. Pulsed electric field (PEF) cardiac ablation has been proposed as a nonthermal technology to cause cell death by irreversible electroporation (IRE). IRE has shown to minimize off target damage. The lack of systematic studies to inform optimal PEF ablation parameters has significantly slowed down device development and regulatory process.

Hypothesis:
As part of a larger effort to develop a standard laboratory assay for PEF parameter optimization, in this study we investigate tissue specificity of IRE cardiac ablation treatments.

Methods:
Human induced pluripotent stem cell cardiomyocytes derived (hiPSC-CMs, Fujifilm Cellular Dynamic, Inc.), human esophageal muscle cells (HESMC, ScienCell Research Laboratories), and human bronchial epithelial cells (HBEC3-KT, ATCC) were cultured in monolayer formats on 96-well NanoFiber plates. PEF were delivered by an FID pulse generator connected to two needle electrodes (1.7 mm center-to-center distance). PEF parameters investigated in this study are: phase duration tp=1, 5, 10 μs; phase intensity Vp=284, 372, 568V; pulse repetition frequency PRF=10, 100, 1000 Hz, pulse number p#=100. We quantified IRE areas 4 hours post-treatment by propidium iodide (PI).

Results:
Preliminary results show that increasing the tp, Vp and decreasing the PRF resulted in a larger IRE area in all the cell types studied. For the range of PEF parameters investigated, a treatment with same tp, p# and PRF required higher Vp to induce IRE in HESMC and HBEC3-KT than hiPSC-CMs, i.e., 100 pulses with tp=5 μs and PRF=1000 Hz, to achieve the same IRE area, hiPSC-CMs needed half Vp than HESMC and HBEC3-KT.

Conclusions:
Our data suggests that same PEF treatments induced larger IRE areas in hiPSC-CM than in HESMC and HBEC3-KT. Future work will focus on validating these results in tissues to assess safety of IRE cardiac ablation devices.
Abstract 13155: Apelin and Apela for Therapy of Myocardial Fibrosis and Heart Failure
Authors: Kemppi Anna , Rahtu-Korpela Lea M , Szabo Zoltan , Raatikainen Sami , Anisimov Andrey , Alitalo Kari K , Magga Johanna , Kerkela Risto
Published: June 2023

The apelin/apela – apelin receptor system regulates a variety of physiological cardiovascular functions including vascular tone, cardiac contractility, angiogenesis, and energy metabolism. However, the cell type specific effects of apelin/apela in the cardiovascular system are not well understood. The aim of this study was to investigate the potential role of apelin and apela in regulating development of myocardial fibrosis and to identify the signaling mechanisms underlying the anti-fibrotic effects. To investigate the role of apelin and apela
in vivo
, 2-month-old C57BL/6N male mice were injected with AAV9.LacZ, AAV9.Apelin or AAV9.Apela and subjected to thoracic aortic constriction (TAC) for 6 weeks. Echocardiography analysis at the end of the study showed that overexpression of either apelin or apela attenuated TAC-induced left ventricular (LV) dysfunction and increase in LV mass. Analysis of cardiac tissue showed downregulation of collagen I and fibrosis related periostin mRNA expression levels and reduced accumulation of interstitial fibrosis in the left ventricles of mice overexpressing apelin or apela. Studies in human cardiac fibroblasts
in vitro
showed that apelin and apela attenuate TGFβ1-induced collagen expression and secretion. Analyses of LV tissue and human fibroblast samples indicated that apelin and apela regulate the stress-induced activation of MAPK pathways. Chemical inhibitors and genetic modification of specific signaling elements identified p38 MAPK as a central signaling pathway mediating the inhibitory effect of apelin and apela on TGFβ1 signaling and TGFβ1-induced collagen production. In summary, we show that apelin and apela attenuate hemodynamic pressure overload -induced LV dysfunction and myocardial fibrosis and identify a novel signaling mechanism regulating the response. Our data suggests that activation of apelinergic signaling could offer a novel therapeutic approach to prevent the development of cardiac fibrosis and heart failure.
Abstract 13173: Impact of Bicuspid Aortic Valve Morphology on Computed Tomography Valvular Calcification in Aortic Stenosis and Sex Differences
Authors: Ye Zi , Clavel Marie-Annick A , Foley Thomas A , Pibarot Philippe , Enriquez Sarano Maurice E , Michelena Hector I
Published: June 2023

Introduction:
Aortic valve calcification (AVC) is the key pathophysiology underlying aortic stenosis (AS). We aimed to assess computed tomography AVC in AS by valve morphology (bicuspid [BAV] vs. tricuspid aortic valve[TAV]) and sex.

Methods:
Retrospective study of patients with echocardiographic AS severity and AVC assessments within six months. Patients with > moderate aortic regurgitation, prosthetic aortic valve, or indeterminate aortic valve morphology were excluded. Severe AS with high mean gradient (MG) was defined as aortic valve area (AVA)≤1cm2 or indexed AVA≤0.6 cm2/m2 + MG≥40 mmHg.

Results:
Of 2647 patients, 361(65% men) had BAV and 2286(59% men) had TAV, age 65±11 vs. 80±9 years(p<0.001), AVA 1.07±0.42 vs. 0.90±0.25 cm2(p<0.001), MG 41±16 vs.42±14 mmHg(p=0.4) for BAV and TAV, respectively. For both BAV and TAV groups, age, MG, and severe AS frequency were similar between women and men(all p≥0.06). BAV morphology affected AVC-AS severity and AVC-sex associations (p for interactions <0.001): as AS severity increased, mean AVC difference became larger between BAV-men and TAV-men, but smaller between BAV-women and TAV-women. Similar patterns were observed in AVC density (AVCd, AVC divided by left ventricular outflow tract diameter)-AS severity and AVCd-sex associations (p for interactions < 0.001). In patients with concordant AS severity and MG levels, the best BAV AVC-cutoff for detecting severe AS + high MG by area-under-the-curve analysis was 924 AU for BAV-women and 2851 AU for BAV-men, different from guideline-recommended AVC-thresholds (1200 for women and 2000 for men). The best BAV AVCd cutoff was 289 for BAV-women and 476 for BAV-men, similar to the cutoffs for patients predominantly with TAV (292 for women and 476 for men from Clavel MA JACC 2013). The BAV-AVC threshold identified more patients with severe AS than guideline-recommended threshold in BAV-women (84% vs 74%, p<0.001), but not in BAV-men.

Conclusions:
Valvular calcium accretion in AS was different by valve morphology and sex. As compared to TAV, BAV-women exhibited the least calcification while BAV-men exhibited the highest. Such patterns may impact the sensitivity of guideline-recommended AVC thresholds for detecting severe AS in BAV patients.
Abstract 13185: Incidence and Risk Factors of Acute Cardiovascular Complications After Hematopoietic Stem Cell Transplantation
Authors: Vasbinder Alexi , Anderson Elizabeth , Catalan Tonimarie , Chu Catherine , Kotzin Megan , Azam Tariq , Perry Daniel , Shadid Husam , Rochlen Matthew , Yentz Sarah , Schneider Bryan , Leja Monika , Lao Christopher , Fecher Leslie , Nathan Sunita , Okwuosa Tochi , Hayek Salim
Published: June 2023

Introduction:
Hematopoietic stem cell transplantation (HSCT) is associated with various cardiovascular (CV) complications. Due to the lack of recent large cohort studies, the incidence and clinical determinants of acute HSCT-related CV events are ill-defined.

Methods:
We conducted a multi-center observational study (University of Michigan and Rush University) of adult (≥18 years) patients who underwent autologous or allogeneic HSCT for malignant or non-malignant bone marrow disorders from 2005-2021. Data on demographics, pre-HSCT clinical characteristics, imaging, laboratory findings, and acute (<100 days post-HSCT) CV outcomes were collected through manual chart review. The primary outcome was defined as a composite of death from CV cause, non-fatal myocardial infarction, need for revascularization, new-onset heart failure (HF), new diagnosis of atrial fibrillation/flutter, or sustained ventricular tachycardia.

Results:
Of 4,262 included patients (mean age at HSCT 56±14 years; 59% male; 82% White), 161 (3.8%) patients experienced an acute CV event (153 events/1,000 person-years). Compared to patients without a CV event, those who developed a CV event were older, had greater burden of CV comorbidities including HF, more likely to be on antihypertensives, statins, and aspirin, and had higher B-type natriuretic peptide and lower high-density lipoprotein pre-HSCT (Table). Pre-HSCT ejection fraction and prior anthracycline exposure were not associated with acute CV events.

Conclusions:
In the largest cotemporary cohort of adult HSCT patients to date, acute CV events occurred in <5% of patients. Events were more common in older patients with CV comorbidities. highlighting the potential need for improving the pre-HSCT CV risk stratification. The major limitation of this study is the retrospective nature and accompanying selection bias. Future prospective studies should assess evidence-based strategies for risk-stratifying HSCT patients.
Abstract 13195: A Case of Ebstein Anomaly Diagnosed Following Tricuspid and Pulmonic Valve Infective Endocarditis in an Adult Patient
Authors: Tsourdinis George E , Hussain Kifah , Minga Iva , Robin Jason C , Pursnani Amit
Published: June 2023

Background:
We present a rare case of infective endocarditis (IE) involving both tricuspid (TV) and pulmonic valves (PV) in the setting of newly diagnosed Ebstein anomaly (EA) with isolated, small membranous VSD.

Case:
A 48 yo woman with no known medical history presented with two weeks of fever, flu-like symptoms, and dyspnea. Vitals showed fever, tachycardia, and tachypnea. Poor dentition, grade III systolic murmur, and S3 gallop were noted on physical exam. EKG showed sinus tachycardia and right bundle branch block. Laboratory studies showed leukocytosis and elevated CRP. A chest CT revealed bilateral lung infiltrates in a rounded configuration concerning for septic emboli. Blood cultures grew
Streptococcus mitis
, and IV antibiotics were initiated. TTE revealed 3.2cm apical displacement of the TV resulting in right ventricular atrialization, diagnostic for EA. TTE also found a 26x17mm vegetation on the septal and anterior leaflets of the TV with moderate tricuspid regurgitation and an 11x6mm vegetation on the PV, confirmed by TEE. Cardiac MRI also noted a focal aneurysm of the membranous interventricular septum with a hemodynamically insignificant shunt.

Discussion:
While interatrial communications are seen in a majority of EA patients (80-94% of cases), this patient presented solely with a small membranous VSD and absence of ASD and PFO. Moreover, this patient had no PDA to depend on for pulmonary flow. Remarkably, she had an asymptomatic course with EA until the development of endocarditis. It is believed the presence of an isolated VSD in this patient’s severe EA likely promoted forward pulmonic flow in an already inadequate right ventricle. Right-sided IE is itself rare (5-10% of cases) with isolated PV involvement being even rarer (2% of cases). This patient’s uncorrected EA with redundant TV and PV leaflet tissue likely contributed as a nidus for simultaneous infection of both valves.
Abstract 13206: Clinical Characteristics, Risk Factors, and Medication Use of Patients Under 50 Presenting With Stemi
Authors: Haq Ayman , Walser-Kuntz Evan , Benson Gretchen A , Miedema Michael
Published: June 2023

Objective:
To examine the clinical characteristics and risk factors of patients with ST-elevation myocardial infarction (STEMI) <50 years old.

Methods:
All patients aged ≤ 50 years from March 2003 to June 2021 were enrolled from the prospective Minneapolis Heart Institute Level 1 STEMI database. Patient demographics, risk factors, comorbidities, medications use, illicit drug use, and lipid panel were analyzed by gender.

Results:
908 patients were enrolled in the study (79.7% male, 88% Caucasian) and a minority had prior coronary artery disease (CAD) (Table 1). Risk factors included tobacco use (69%) and a family history of CAD (47%). Illicit drug use was rare (Table 2). Use of preventive medications was infrequent, including in those with established risk factors (Table 3). Median lipid levels were only mildly abnormal (Table 4).

Conclusion:
In younger patients with STEMI, smoking remains highly prevalent, rates of preventative medication use are low, and lipid levels alone may not effectively provide risk stratification.
Abstract 13225: Frailty Screening at Scale Using Core Clinical Data and Supervised Machine Learning
Authors: Fountotos Rosie , Afilalo Jonathan
Published: June 2023

Introduction:
Frailty is a major risk factor for adverse health events in older adults with cardiovascular disease.

Hypothesis:
We sought to develop and validate a predictive model leveraging data available in the electronic health record to screen for frailty as defined by a prospective reference standard.

Methods:
We conducted a population-based cohort study using data from the Canadian Longitudinal Study of Aging (CLSA). From 2010-2015, the CLSA enlisted a diverse and multi-ethnic sample of community-dwelling adults 45-85 years of age. Comprehensive phenotyping was performed through interviews at participants’ homes and assessments at data collection sites. Frailty was quantified by the 47-item Frailty Index (FI) Examination, consisting of tests for age-related deficits in physical performance, body composition, cardiovascular and pulmonary physiology, cognitive and sensory function. After dividing our sample into training (80%) and test (20%) sets, we compared machine learning and linear regression models to predict the FI based on age, sex, comorbidities, and blood test results. We used the H2O AutoML platform (DAI 1.10.2) to iteratively determine the optimal model.

Results:
The cohort consisted of 30,097 adults with a mean age of 63±10 years and 51% females. The mean FI score was 0.28±0.08 (best-worst 0.07-0.70). The gradient-boosted machine learning model achieved an R
2
of 0.512 and a root mean squared error (RMSE) of 0.058 to regress FI scores, and an area under the curve of 0.766 to classify FI quintiles, selecting the following 10 variables in descending order of importance: age, chronic heart failure, hypertension, glycated hemoglobin, high-sensitivity C-reactive protein, high-density lipoprotein, red cell distribution width, vitamin D, female sex, and diabetes. The linear regression model achieved a similar R
2
and RMSE with all 62 input variables and a modest decline after selecting the top 10 input variables using a leaps-and-bounds algorithm.

Conclusions:
Frailty screening can be performed at scale for clinical or research purposes using common clinical and biochemical inputs. Our machine learning model predicted frailty with a manageable number of inputs and yielded pathophysiological insights about their relative importance.
Abstract 13230: Prevalence, Trends, and Outcomes of Cardiovascular Diseases in Pregnant Patients in the United States: 2010 to 2019
Authors: Majmundar Monil , Doshi Rajkumar P , Zala Harshvardhan , Patel Kunal N , Kumar Ashish , Kalra Ankur
Published: June 2023

Introduction:
Contemporary data on the prevalence, trends, and outcomes of cardiovascular diseases (CVD) in pregnant patients are limited.

Hypothesis:
We aimed to analyze the prevalence, trends, and outcomes of CVD and their subtypes in hospitalized pregnant patients in the United States (U.S.).

Methods:
This retrospective population-based cohort study used the Nationwide Readmission Database to identify all hospitalized pregnant patients from January 1, 2010, to December 31, 2019. Pregnancy-associated hospitalizations were identified, and patients with missing information on the length of stay (LOS) and mortality were excluded. Main outcomes were prevalence and trend of CVD burden in pregnant patients.

Results:
39,212,104 hospitalized pregnant patients were identified: 4,409,924 with CVD (11.25%) and 34,802,180 without CVD (88.75%). The annual CVD burden increased from 9.49 % in 2010 to 15.54 % in 2019 (p<0.001). Hypertensive disorder of pregnancy (1069/10,000) was the most common, and aortic dissection (0.1/10,000) was the least common CVD. Trends of all CVD subtypes increased; however, the trend of valvular heart disease decreased. In-hospital mortality was 8.2/10,00 in CVD but its trend decreased from 8.9/10,000 in 2010 to 7.4/10,000 in 2019 (p<0.001). CVD was associated with higher odds of mortality compared with non-CVD patients (odds ratio (OR): 32.7, 95% CI 28.8-37.1, p<0.001). CVD was associated with higher 6-week postpartum readmission (OR: 1.97, 95% CI: 1.95-1.99), myocardial infarction (OR: 3.04, 95% CI: 2.57-3.59), and stroke (OR: 2.66, 95% CI: 2.41-2.94) (p<0.001 for all).

Conclusions:
Overall CVD burden is high among pregnant patients with a significant uptrend of CVDs from 2010 to 2019 in the U.S. CVD burden was associated with higher in-hospital mortality, and 6-week postpartum all-cause readmission, myocardial infarction, and stroke. However, mortality among CVD patients decreased from 2010 to 2019 in the U.S.
Abstract 13234: Prediabetes, an Important Predictor of Major Adverse Cardiac and Cerebrovascular Events in Atrial Fibrillation Patients: A National Inpatient Sample Analysis, 2019
Authors: Desai Rupak , Pingili Adhvithi , Katukuri Nishanth , Sanku Koushik , TAJDIN BORZOO , Cherukuri Akhila S , JALILI HAMIDREZA , Zahdeh Tamer , Bahadoran Pooriya , Srikanth Sashwath
Published: June 2023

Background:
Prediabetes is an established risk factor for major adverse cardiac and cerebrovascular events (MACCE). However, the association between prediabetes (pDM) and MACCE in atrial fibrillation (AF) patients remains understudied. We aim to establish a relation between prediabetes and MACCE in AF patients.

Methods:
Using the National Inpatient Sample (2019) and relevant ICD-10 codes, we identified hospitalizations with AF and categorized them into groups with and without pDM excluding diabetics. The primary outcome was MACCE (All-cause inpatient mortality, Cardiac Arrest including Ventricular Fibrillation, and Stroke) in AF-related hospitalizations.

Results:
Of 2,965,875 AF-related hospitalizations for MACCE, 47,505 (1.6%) were among pre-diabetics. The pDM cohort was relatively younger (median 75 vs 78 years), often consisted of males (56.3% vs 51.4%), blacks (9.8.% vs 7.9%), Hispanics (7.3% vs 4.3%), and API (4.7% vs 1.6%) than the nonprediabetic cohort (p<0.001). The pDM group often had significantly higher rates of HTN, hyperlipidemia, smoking, obesity, drug abuse, prior MI, PVD, and hyperthyroidism (all p<0.05). The pDM cohort was often discharged routinely (51.1% vs 41.1%) but more frequently required home health care (23.6% vs 21.0%) and had higher costs. After adjusting for baseline characteristics or comorbidities, pDM cohort with AF admissions showed higher rate and significantly higher odds of MACCE vs Non-pDM cohort (18.6% vs. 14.7%, OR 1.34, 95CI 1.26-1.42, p<0.001). On subgroup analyses, Males had stronger association (aOR 1.43) compared to females (aOR 1.22) whereas on race-wise comparison, Hispanics (aOR 1.43) and Asians (aOR 1.36) had stronger association with MACCE with pDM vs. whites (aOR 1.33) and blacks (aOR 1.21).

Conclusions:
We found a significant association between prediabetes and MACCE in AF patients. There is a need for further research to actively screen and manage pDM in AF to curtail MACCE.
Abstract 13236: Equitable Policy Lever? : State Minimum Wage Increases and Black - White Disparities in Hypertension
Authors: Brown-Podgorski Brittany L
Published: June 2023

Introduction:
Non-Hispanic Black adults are disproportionately burdened by hypertension compared to White adults. Because Black adults are overrepresented in lower-wage occupations - and lower income is associated with elevated risk of hypertension - minimum wage increases have been explored as a potential policy lever to address Black-White disparities in hypertension. States have the authority to increase minimum wages for workers in their jurisdiction; and 31 states have exercised this authority. However, research suggests that minimum wage increases may have no significant impact on health among Black adults due to “diminished gain” of health effects from socioeconomic resources. This study examines whether Black-White disparities in hypertension persist after states increase minimum wage limits.

Methods:
This study merged state-year minimum wage data from the US Department of Labor with pooled cross-sectional survey data from the Behavioral Risk Factor Surveillance System to assess the relationship between state-level minimum wage increases and Black-White disparities in hypertension over time (2001 - 2019). Separate difference-in-difference models were estimated to individually compare the odds of hypertension among Black and White adults in states with and without minimum wage increases. A difference-in-difference-in-difference model estimated whether minimum wage increases had a differential impact on the odds of hypertension among Black adults compared to White adults.

Results:
Compared to Black and White adults in states without minimum wage increases, both Black (OR= 0.86; p-value=0.04) and White (OR= 0.86; p-value=0.02) adults had a significantly lower odds of hypertension following state increases in the minimum wage. However, the Black-White disparity in hypertension significantly increased following minimum wage increases (OR= 1.50; p-value<0.001).

Conclusions:
These findings suggest that minimum wage increases may benefit White adults significantly more than Black adults, resulting in an increased Black-White disparity in hypertension. As such, increasing minimum wage alone may not be an
equitable
policy approach to address this disparity.
Abstract 13255: Variation in the Use of Therapeutic Hypothermia for Cardiac Arrest
Authors: Wolfe Jonathan D , Fanous Erika , Waken RJ , Fox Daniel , Joynt Maddox Karen E
Published: June 2023

Introduction:

Therapeutic hypothermia is a guideline-recommended treatment for certain unresponsive patients after a cardiac arrest. However, the degree to which patients with cardiac arrest have access to this therapy on a national level is unknown. Understanding hospital- and patient-level factors associated with receipt of hypothermia could inform interventions to improve access to this treatment among appropriate patients.

Methods:

This was a retrospective analysis using National Inpatient Sample data from 2016-2019. We used ICD10 diagnosis and procedure codes to identify adult patients with in-hospital and out-of-hospital cardiac arrest and receipt of therapeutic hypothermia. We used logistic regression with GEE clustering on hospital-year, and controlling for medical comorbidities, to evaluate patient and hospital factors associated with receiving therapeutic hypothermia.

Results:

We identified 478,419 patients (unweighted) with cardiac arrest. Of those, 4088 (0.85%) received therapeutic hypothermia. There was significant regional variation in hypothermia capabilities (Figure 1). At the patient level, age > 74 (OR: 0.54, p<0.001), female gender (OR: 0.89, p>0.001) and Hispanic race (OR: 0.69, p<0.001) were all associated with decreased odds of receiving hypothermia. Compared to patients with private insurance, patients with Medicare (OR: 0.73, p<0.001) and Medicaid (OR: 0.88, p=0.013) were less likely to receive hypothermia. Patients with shockable rhythms were less likely to receive hypothermia than those with non-shockable rhythms (OR: 0.85, p<0.001).

Conclusions:

Therapeutic hypothermia is rarely utilized after cardiac arrest and there is substantial regional variation in its use. Advanced age, female gender, Hispanic race, Medicare or Medicaid insurance, and shockable rhythm are all associated with a decreased likelihood of receiving hypothermia.
Abstract 13258: Myosin Light Chain Dephosphorylation by Ppp1r12c Promotes Atrial Hypocontractility in Atrial Fibrillation
Authors: Gonzalez Francisco , perike srikanth , Damen Frederick W , Capote Andrielle , Alsina Katherina M , Levin Benjamin , Sridhar Arvind , Grand Jacob , Martin Jody , Akar Joseph , Warren Chad M , Solaro R John , Darbar Dawood , Goergen Craig J , Wolska Beata M , Wehrens Xander H , McCauley Mark
Published: June 2023

Introduction:
Atrial fibrillation (AF) is the most common sustained arrhythmia, with an estimated prevalence in the U.S. of 6.1 million . AF increases the risk of a thromboembolic stroke in five-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function in AF remains unknown. We have recently identified protein phosphatase 1 subunit 12c (PPP1R12C) as a key molecule targeting myosin light chain phosphorylation in AF.

Objective
We hypothesize that the overexpression of PPP1R12C causes hypophosphorylation of atrial myosin light chain 2 (MLC2a), thereby decreasing atrial contractility in AF.

Methods and Results
Left and right atrial appendage tissues were isolated from AF patients versus sinus rhythm (SR). To evaluate the role of the PP1c-PPP1R12C interaction in MLC2a de-phosphorylation, we utilized Western blots, co-immunoprecipitation, and phosphorylation assays. In patients with AF, PPP1R12C expression was increased 3.5-fold versus SR controls with an 88% reduction in MLC2a phosphorylation. PPP1R12CPP1c binding and PPP1R12C-MLC2a binding were significantly increased in AF. In vitro studies of either pharmacologic (BDP5290) or genetic (T560A) PPP1R12C activation demonstrated increased PPP1R12C binding with both PP1c and MLC2a, and dephosphorylation of MLC2a. Additionally, to evaluate the role of PPP1R12C expression in cardiac function, mice with lentiviral cardiac-specific overexpression of PPP1R12C (Lenti-12C) were evaluated for atrial contractility using echocardiography, versus wild-type and Lenti-controls. Lenti-12C mice demonstrated a 150% increase in left atrium size versus controls, with reduced atrial strain and atrial ejection fraction. Also, programmed electrical stimulation was performed to evaluate AF inducibility in vivo. Pacing-induced AF in Lenti-12C mice was significantly higher than controls.

Conclusion
The overexpression of PPP1R12C increases PP1c targeting to MLC2a and provokes dephosphorylation, associated with a reduction in atrial contractility and increase in AF inducibility. All these discoveries suggest that PP1 regulation of sarcomere function at MLC2a is a main regulator of atrial contractility in AF.
Abstract 13262: Phytosterol Intake and Risk of Coronary Heart Disease in U.S. Men and Women
Authors: Wang Yeli , Hu Yang , Sampson Laura , Manson Joann E , Rimm Eric B , Sun Qi
Published: June 2023

Introduction:
Phytosterols are structurally similar to cholesterol and partially inhibit intestinal absorption of cholesterol. Evidence regarding dietary phytosterols in relation to coronary heart disease (CHD) risk remains limited. We aimed to prospectively assess the associations between total and individual phytosterol intake and CHD risk in U.S. men and women.

Methods:
A total of 214,108 men and women from the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study without cardiovascular disease or cancer at baseline were included in the analyses. Diet was assessed using a validated food frequency questionnaire every 2-4 years since baseline. Cox proportional hazards regression models were used to evaluate associations between phytosterol intake and CHD risk.

Results:
During 5,516,455 person-years of follow-up, 10,152 CHD cases were documented. Comparing extreme quintiles, pooled hazard ratios (HRs) (95% CIs) of CHD were 0.91 (0.85-0.98;
P
-trend=0.08) for total phytosterols, 0.88 (0.82-0.95;
P
-trend=0.02) for campesterol, 0.96 (0.90-1.02;
P
-trend=0.22) for stigmasterol, and 0.91 (0.84-0.98;
P
-trend=0.03) for beta-sitosterol. Nonlinear associations were observed for total phytosterols, campesterol, and beta-sitosterol: the risk reduction plateaued at intakes above ~180 mg/day, 30 mg/day, and 130 mg/day, respectively (
P
-nonlinearity<0.001). Among 23,543 participants with existing CHD risk markers, phytosterol intake was inversely associated with plasma levels of total cholesterol, triglycerides, C-reactive protein, and interleukin-6, and was positively associated with adiponectin. Phytosterol intake was not associated with LDL or HDL cholesterol levels.

Conclusions:
Higher long-term intake of total and major subtypes of phytosterols was associated with modest CHD risk reduction, which may plateau at moderate intake levels. The role of phytosterols in preventing CHD needs further investigation.
Abstract 13292: Rural-Urban Differences in Mortality Rate of Myocardial Infarction and Heart Failure: A Systematic Review and Meta-Analysis
Authors: Shurrab Mohammed , Ko Dennis T , Atoui Rony , Costa Vitali Atilio , Abu Shama Raed , alnasser Sami , Narendrula Rashmi , Papadopoulos Gregory , Kerr Mary Catherine , McIsaac Sarah , Abdel Qadir Husam , Healey Jeff S , Henderson Mark
Published: June 2023

Introduction:
Studies indicate that living in a rural area may be associated with worse health outcomes. However, it is unclear whether rurality is associated with mortality in patients with acute myocardial infarction (AMI) and heart failure (HF). This systematic review and meta-analysis aimed to evaluate rural-urban differences in mortality rate after AMI or HF.

Methods:
A systematic search was conducted for studies published till May 1, 2022 in PubMed, Embase and CENTRAL. Included studies compared mortality rates after hospital admission for AMI or HF in rural versus urban areas. Follow up ranged between 30 days and 3 years. Adjusted Odds ratios (aORs) were pooled with a random-effects model.

Results:
Six cohort studies were identified, which included 785,156 patients (128,990 in rural vs. 656,166 in urban) with AMI and 1,159,000 patients (192,749 in rural vs. 966,251 in urban) with HF. Compared with urban, patients admitted with AMI in rural areas had higher mortality rates (16% vs 14%, aOR 1.12, 95% Confidence Interval (CI) 1.05-1.20;
p
=0.0003,

I
2

=75%). Compared with urban, patients admitted with HF in rural areas had higher mortality rates (21% vs 18%, aOR 1.19, 95% CI 1.03-1.38;
p
=0.02,

I
2

=90%). (Figure)

Conclusions:
Among patients with AMI or HF, living in rural areas is associated with an increased risk of mortality. Clinical and policy efforts are needed in order to reduce disparities in rural health.
Abstract 133: Association Between Bystander Physical Limitations And Delays In Chest Compression During T-CPR
Authors: Missel Amanda L , Drucker Christopher , Kume Kosuke , Shin Jenny , Neumar Robert W , Kudenchuk Peter J , Rea Thomas
Published: June 2023

Background:
Promptly initiated bystander cardiopulmonary resuscitation (CPR) improves survival from out-of-hospital cardiac arrest (OHCA). Many OHCA patients require repositioning (e.g., moved to hard surface) to improve chest compression (CC) quality, which can delay CC. We examined the association between repositioning, CC delay, and patient outcomes.

Methods:
We used quality improvement data from review of 911 dispatch audio recordings of OHCA in adults eligible for telephone CPR (T-CPR) in King County, WA between 2013 and 2021. OHCA was categorized into 3 groups: CC not delayed, CC delayed due to bystander-reported physical limitations to reposition the patient, or CC delayed for other reasons. The primary outcome was delay in CC defined as the interval between start of T-CPR instructions and CC onset. We performed Kruskal-Wallis and Chi Square tests to evaluate global differences and post-hoc analyses with Bonferroni correction for pairwise differences.

Results:
Of the 3,483 OHCA patients eligible for T-CPR, median age was 64, 35% were women, 45% were witnessed, 23% had an initial shockable rhythm, and 15% survived to discharge. T-CPR was not delayed between instructions and compressions in 1,618 patients (46%), was delayed due to bystander physical limitations in repositioning the patient in 1,218 (35%), and was delayed for other reasons in 647 (19%). The interval from T-CPR instruction to CC onset was longest for the physical limitations delay group (121 secs, IQR: 69) compared to the other delay group (88 secs, IQR: 65) and the no delay group (54 secs, IQR: 36) (all comparisons p<.05). Bystander CPR was less frequent in the physical limitations delay group (74%) versus no delay (100%) or the other delays group (81%, all comparisons p<.05). In the physical limitation delays group, 154 (13%) of patients ultimately received bystander CPR on a soft surface (e.g., bed). This group also had the lowest hospital discharge survival (11%, p<.05) versus the no delays (17%) and other delays group (17%).

Conclusion:
Bystander physical limitations are a common barrier to repositioning patients to begin CPR. Repositioning delays were associated with lower likelihood of receiving CPR, longer times to begin CC, and lower survival rates.