bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16626: Optical Coherence Tomography Guided Percutaneous Coronary Intervention is Not Associated With Decline in Kidney Function
Authors: Nemoto Teruyoshi , Minami Yoshiyasu , Sato Toshimitsu , Muramatsu Yusuke , Kakizaki Ryota , Hashimoto Takuya , Fujiyoshi Kazuhiro , Oikawa Jun , Meguro Kentaro , Shimohama Takao , Tojo Taiki , Ako Junya
Published: April 2024

Introduction:
Optical coherence tomography (OCT) guided percutaneous coronary intervention (PCI) may increase the contrast volume. However, the impact of OCT-guided PCI on the incidence of decline in kidney function (DKF) in real-world clinical practice had not been fully evaluated.

Methods:
Among a total of 1,003 consecutive patients who underwent PCI in our institute, we identified 201 propensity score matched pairs adjusted by baseline factors for DKF with either OCT-guided or intravascular ultrasound (IVUS)-guided PCI. The incidence of DKF was compared between the two groups. Patients on hemodialysis were excluded from the analysis. DKF was defined as an increase in serum creatinine level ≥0.5 mg/dl or the relative increase with ≥25% from the baseline value within 48 hours or one month after the PCI.

Results:
The baseline clinical characteristics including the prevalence of chronic kidney disease (CKD) (52 vs. 49%, P=0.62) were comparable between the groups. There was no significant difference in contrast volume between the OCT group and the IVUS group (148 vs. 142 ml, P=0.29) though it was significantly greater in the OCT group in cases of acute coronary syndrome (ACS) (175 vs. 156 ml, P=0.026). The incidence of DKF was comparable between the two groups at both 48 hours (0.5% vs. 2%, P=0.37) and one month (4% vs. 8%, P=0.14) after the PCI. Multivariate analysis demonstrated that diabetes (odds ratio [OR] 2.74, 95% confidential interval [CI] 1.18-6.37, P=0.02), ACS (OR 4.13, 95% CI 1.71-9.96, P<0.01) and age (≥70 years old; OR 4.55, 95% CI 1.65-12.6, P<0.01) were the predictors for DKF at either 48 hours or one month.

Conclusions:
OCT-guided PCI did not increase the incidence of DKF as compared with IVUS-guided PCI in real-world clinical practice.
Abstract 16631: Frailty Phenotype is Associated With 1-Year Outcomes in Ambulatory Advanced Heart Failure: A Report From the REVIVAL Registry
Authors: Lala Anuradha , Shah Palak , Cooper Lauren , Mountis Maria , Robinson Shawn W , Lanfear David , Estep Jerry D , Jorde Urlich , Jeffries Neal , Stevenson Lynne W , Khalatbari Shokoufeh , Spino Catherine A , Richards Blair , Mann Douglas , Stewart Garrick C , Aaronson Keith D
Published: April 2024

Introduction:
The Fried Frailty Phenotype (FFP), defined by weakness, slowness, inactivity, exhaustion and weight loss, predicts adverse outcomes in geriatric populations but has not been studied in advanced heart failure (AHF). The REVIVAL study prospectively collected frailty measures in ambulatory patients with advanced HF to determine relevant components of frailty in this population and the impact on clinical outcomes.

Hypothesis:
We hypothesize that measures of frailty will be strongly associated with the 1 yr composite outcome of LVAD, UNOS 1A/ B cardiac transplant or death.

Methods:
The REVIVAL registry enrolled ambulatory patients with AHF on oral Rx (INTERMACS Profiles 4-7). A modified FFP was defined by 5 components:1) weakness: hand grip strength <25% of body weight; 2) slowness: 5-m gait time <6 seconds; 3) weight loss > 10lbs in the past yr; 4) inactivity from 5 Kansas City Cardiomyopathy Questionnaire (KCCQ) activity questions and 5) exhaustion from 2 KCCQ exhaustion questions. A score of 0-1 was deemed not frail, 2 was pre-frail, and ≥3 was considered frail. Event-free survival for each group was determined by the Kaplan-Meier method and the increased hazards of pre-frailty and frailty compared to non-frailty were determined with proportional hazards modeling.

Results:
Frailty was present in 18% of the 335 patients with complete 5-component FFP data, pre-frailty in 41%, and non-frailty in 41%. During the first year, 89 outcome events occurred, with HR 2.5 (p=0.003, 95% CI 1.4, 4.7) in frail, and HR 1.8 (p=0.029, 95% CI 1.1, 3.2) in the pre-frail, compared to non-frail patients. (Figure)

Conclusions:
Using the Fried Frailty criteria to classify patients as frail, pre-frail and not-frail helped to identify patients with ambulatory HF at high risk for death, LVAD or transplant at 1 year. Assessment of frailty can improve triage for advanced HF therapies, inform our understanding of comparative outcomes with transplant, LVAD or continued medical therapy.
Abstract 16640: 2D Echocardiography Correlation Data Among Different Clinical Diseases
Authors: Yousef George M , Abraham Nader G , Thompson Ellen , Shapiro Joseph I
Published: April 2024

Introduction:
Different systemic disease affect the heart to varying degrees. However traditional echocardiographic parameters are somewhat limited with respect to sensitivity and specificity.

Methods:
Retrospective chart view of 98 patients in our Echo lab. Clinical and echocardiographic data were obtained. Correlation analysis was performed using the R programming language examining the impact of Diabetes Mellitus (DM), Coronary Artery Disease (CAD), Hypertension, and Chronic Kidney Disease (CKD) on correlations between variables.

Results:
18.3% (N=18) patients have underlying CKD. In comparison between patients with and without CKD, there was a significant difference in in the correlation between measurements specifically involving those between blood pressure, ventricular architecture and diastolic function (see attached heatmaps). Conversely, there was no significant difference noted in patients with and without DM, CAD, or HTN.

Conclusions:
Certain correlations between clinical and echocardiographic data are significantly impacted in patients with chronic kidney disease. This suggests that comparing the ratio or product of these measurements might create new indices to track the development and/or progression of the cardiomyopathy associated with CKD.
Abstract 16643: Clinical Implications of Identifying Pathogenic Variants in Aortic Dissection Patients With Whole Exome
Authors: Yang Bo , Wolford Brooke , Hornsby Whitney E , Guo Dongchuan , Zhou Wei , Lin Maoxuan , Farhat Linda , McNamara Jennifer , Driscoll Anisa , Wu Xiaoting , Schmidt Ellen , Brummett Chad , Patel Himanshu J , Eagle Kim A , Milewicz Dianna M , Kitzman Jacob , Willer Cristen J
Published: April 2024

Introduction:
Aortic dissection is a life threatening condition due to associated complications, such as aortic rupture, end-organ malperfusion and failure with high mortality of surgical treatment. It is not known how to manage family members of patient’s that suffer from aortic dissection, and routine cascade genetic screening of first-degree family members is not regularly practiced.

Hypothesis:
Clinical genetic testing for patients and cascade screening would identify pathogenic variants facilitating the management of patients with aortic dissection and families.

Methods:
From August 2012 to December 2015, 265 patients with aortic dissection had whole exome sequencing (WES), including Stanford type A and B or rupture, at Michigan Medicine with age-, sex-, and ancestry-matched controls (n=265). After quality control, 249 non-trauma dissection cases and 258 controls were retained. Annotation of variants in 11 known genes lead to heritable thoracic aortic disease (HTAD) was performed by experts in the field blinded to sample’s case or control status. Non-pathogenic variants were identified in 223 patients and pathogenic variants were in 26 patients.

Results:
Twenty-four pathogenic variants across 6 genes (
COL3A1, FBN1, LOX, PRKG1, SMAD3, TGFBR2
) were identified in 26 patients representing 10% of aortic patients and 0% of controls. Compared to non-pathogenic group, the pathogenic group was significantly younger (41 vs 57 years, 77% younger than 50 years old), more root aneurysm (54% vs 29%), less hypertension (15% vs. 57%) and smoking history (19% vs. 47%), and more incidence of TAAD in parents, siblings and children. (all p’s<0.05)

Conclusion:
We recommend clinical genetic testing of known HTAD genes in patients of aortic dissection with subsequent cascade screening of family members, especially the age of onset of aortic dissection younger than 50 years old, with aortic root aneurysm, no history of hypertension and smoking, as well as family members of patients whose causative variants have been identified. If the patient and families are found to have the known pathologic HTAD genes, then surgeons should be more aggressive to perform prophylactic operation on those patients to prevent aortic dissection.
Abstract 16645: Comparison of Primary Care Providers and Pediatric Cardiologists in the Appropriateness Use Criteria and Associated Cost Differences for Outpatient Pediatric Echocardiograms
Authors: Fernandes Benedicto A , Thompson Tracey M , Hasselman Ty E , Jantzen David
Published: April 2024

Introduction:
Appropriate use criteria (AUC) have been established for the transthoracic echocardiogram (TTE) in pediatric cardiology, but, in many labs, echocardiograms can be ordered by the primary care provider (PCP). There is limited data comparing appropriateness between pediatric cardiologists and PCPs and the associated costs of rarely appropriate echocardiograms.

Hypothesis:
Pediatric cardiologists order less rarely appropriate TTEs and have a lower proportion of cost attributed to rarely appropriate studies.

Methods:
Patients with initial outpatient pediatric or congenital TTE ordered by a pediatric cardiologist or PCP and interpreted at our institution from November 2016 to October 2017 were included. Appropriateness of TTE indications were classified as appropriate, maybe appropriate, rarely appropriate, and unclassifiable. TTE findings were classified as normal, incidental or abnormal. TTE cost was estimated using the Healthcare Bluebook. The sum cost of rarely appropriate TTEs was divided by total number of patients in each group (pediatric cardiologists vs. PCPs). Data was compared using chi-squared testing.

Results:
311 pediatric cardiology and 193 PCP patients were included for analysis. Two percent of pediatric cardiology and 18% of PCP TTE indications were unclassifiable. Of those classified, pediatric cardiologists had a higher rate of appropriate TTEs compared to PCPs (69% vs. 35%; p<0.001) and lower rate of rarely appropriate TTEs (17% vs. 62%; p<0.001). Abnormalities were present in 13% of TTEs ordered by pediatric cardiologists compared to 3% ordered by PCPs (p<0.001). Based on cost of $526 per TTE, $326
per patient
was attributed to rarely appropriate indications when ordered by PCPs compared to $90 per patient for pediatric cardiologists. This cost difference decreases substantially when taking referral and ECG costs into account ($326 vs $273).

Conclusions:
PCPs order more rarely appropriate TTEs, and subsequently have a higher cost incurred per TTE for rarely appropriate indications. However, this cost difference decreases substantially when taking into account referral and ECG costs. Therefore, PCP education of the AUC would have a significant impact in reducing cost for rarely appropriate indications.
Abstract 16651: Diuretic Responsiveness and Its Prognostic Importance in Children With Heart Failure
Authors: Price Jack F , Younan Samuel , Cabrera Antonio , Denfield Susan , Tunuguntla Hari , Choudhry Swati , Dreyer William , Akcan-Arikan Ayse
Published: April 2024

Introduction:
Fluid overload and congestion are common features of acute decompensated heart failure (ADHF) in children. However, response to diuretics is variable and, in adults, may predict outcome. We sought to identify risk factors for and prognostic relevance of decreased diuretic responsiveness (DR) in children hospitalized with ADHF.

Hypothesis:
We hypothesized that diminished diuretic responsiveness is associated with worse clinical outcomes.

Methods:
We performed a single center, retrospective cohort study, examining the medical records of 197 consecutive children <21 years of age who were hospitalized with ADHF. Patients receiving thiazide diuretics were excluded. DR was defined as net fluid (mL) output per 1mg of furosemide equivalents during the first 72 hours of treatment with a loop diuretic. Greater and lesser DR was determined by DR values above and below the median, respectively. Multivariable analysis was performed to determine association of DR with the composite end-point of inpatient death or need for mechanical circulatory support (MCS).

Results:
A total of 119 patients (51% female) met study criteria. Median age at admission was 6.7 years (IQR 1.6 to 14.2 years). Etiologies of ADHF included dilated cardiomyopathy (n=73), congenital heart disease (n=16), acute heart transplant rejection (n=10), myocarditis (n=9), restrictive cardiomyopathy (n=7), hypertrophic cardiomyopathy (n=1), and ischemic cardiomyopathy (n=1). Median ejection fraction was 26% (IQR 18-38%). Median DR was 5.8 ml/mg (IQR -3.6 to 15.3 ml/mg). Thirty-four percent of patients remained in a positive fluid balance after 72 hours of treatment with a loop diuretic. Factors associated with lesser DR included: younger age, the absence of peripheral edema, female sex and the use of inotropes. The composite end-point of death or MCS occurred in 31 (26%) patients. Lesser DR was associated with worse outcomes, even after adjusting for age and total urine output per weight (OR 6.9, p<0.01). Patients with lesser DR also experienced longer length of hospital stay than patients with greater DR (median, 55 vs 27 days, p<0.01).

Conclusions:
In children hospitalized with ADHF, early diminished DR during decongestion therapy is common and portends a poor prognosis.
Abstract 16691: Racial Differences in Heart Failure With Preserved Ejection Fraction: A Proteomic Analysis
Authors: Sanchez Cynthia L , Njoroge Joyce , Swat Stan A , Shah Sanjiv J
Published: April 2024

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is common in African Americans (AAs). AAs with HFpEF tend to have lower natriuretic peptide levels, higher body mass index, worse hypertension, and higher risk for HF hospitalization than whites with HFpEF. Whether the underlying pathogenesis of HFpEF in AAs is different than whites is unclear.

Hypothesis:
Proteomic analysis could identify novel proteins that differ by race/ethnicity among HFpEF patients.

Methods:
129 HFpEF patients (LVEF >50% and elevated LV filling pressures by invasive hemodynamics, echocardiography, or BNP > 100 pg/ml) were prospectively enrolled. Race/ethnicity was ascertained by self-report, and patients were stratified into 2 groups (AAs [n=23] and whites [n=94]), with the remaining patients (n=12) excluded. Biomarkers were quantified using the Olink antibody-based proximity extension assay technique (CVD2, CVD3, and inflammation panels). Each of the 276 biomarkers were compared between groups (AAs vs. whites) using multivariable logistic regression analysis adjusted for age, sex, BMI, hypertension, and creatinine. P-values were adjusted for multiple comparisons using false discovery rate (FDR). Principal component analyses (PCA) analyses were also used to analyze biomarker data.

Results:
Mean age was 70±12, 58% were female, and 20% were AA. History of HTN was more common in AAs compared to whites (96% vs. 72%, p=0.014); comorbidities were otherwise similar between the 2 groups. On multivariable analysis, 13/276 biomarkers were significantly different between groups after FDR correction: PSGL1, CXCL1, PRSS8, RAGE, CCL15, IL18, CPB1, CXCL5, BDNP, XCL1, THBS2, IL18, and CCL23. The top hit (PSGL1, P-selectin glycoprotein ligand 1), was significantly different between AAs and whites after multivariable adjustment (p=1.2 x 10
-9
). PSGL1 is involved in the binding of cell adhesion molecules to the endothelium and white blood cells. Prior (non-HF) studies have found that RAGE (receptor for advanced glycation endproducts) levels are lower in AAs than whites, and low RAGE is associated with a number of chronic diseases. Of the top 10 principal components, 4 were significantly different between whites and AAs after multivariable adjustment, suggesting that groups of proteins differ between AAs and whites.

Conclusions:
On proteomic analyses, there are significant differences in circulating biomarkers between AAs and whites with HFpEF. If validated, these data may provide insight into racial differences in HFpEF pathogenesis and outcomes.
Abstract 16703: Regulation of Cell Proliferation in Renal Injury by Dopamine D2 Receptors
Authors: Kumar Megha , Asico Laureano , Konkalmatt Prasad , Freyberg Zachary , Jose Pedro A , Armando Ines
Published: April 2024

Introduction:
Genetic factors contribute to the susceptibility to chronic renal disease associated with essential hypertension. The renal dopamine D2 receptor (D2R) has a significant role in blood pressure (BP) control and in negative regulation of the development of inflammation and injury. Several common single nucleotide polymorphisms of the human
DRD2
gene are associated with decreased D2R expression and function. Impaired D2R function results in renal inflammation and end-organ damage. Injury to the kidney triggers a cell proliferation response that can be either adaptive, leading to repair of the tubular epithelium, or maladaptive, leading to fibrosis and chronic kidney disease.

Hypothesis:
We tested the role of renal D2Rs in the cell proliferation response

Methods:
We used models of renal injury in mice and human renal proximal tubule cells (hRPTCs)

Results:
Renal selective silencing of the D2R in mice resulted in an increase in the mRNA expression of the proliferation marker Ki-67 (2.8±0.8 vs 1.0±0.1 fold; qRT-PCR; P<0.05; n=4-5), along with an increase in the number of proliferating cells in renal cortical slices determined by nuclear Ki-67 staining (36±3 vs 6±1; positive cells/field; P<0.05), in comparison with mice with no silencing. Renal tubule-selective rescue of D2R function in these mice by the ureteral infusion of AAV carrying D2R reduced the expression of cortical Ki-67 mRNA (42±3 vs 100±5 %; P<0.05; n=4) and the number of positive cells/field (16±2 vs 32±5; P<0.05), in comparison with mice treated with a control AAV. In mice subjected to renal ischemia reperfusion Ki-67 mRNA expression was higher (1.5±0.03 vs 1.0±0.05 fold; P<0.05; n=3-4) than in mice with sham operation. Renal tubule treatment with AAV carrying D2R after ischemic injury reduced Ki-67 expression (0.65±0.05 vs 1±0.1; P<0.05) and the number of Ki-67 positive cells in kidney sections. Rescue of function or renal tubule-selective D2R overexpression reduced tissue damage, fibrosis and the increase in BP in these models. Treatment of hRPTCs with the nephrotoxic, aristolochic acid (5 μg/ml, 24h), increased mRNA Ki-67 (2.8±0.2 fold; P<0.05; n=4-5) in comparison with cells treated with vehicle while the presence of a D2R agonist, quinpirole (1μM, 24h), in the medium reduced the increase by 42% and also reduced the increase in fibronectin 1 and collagen 1a1 elicited by aristolochic acid

Conclusions:
Our data suggest that regulation of cell proliferation is one of the mechanisms involved in the protective effect of D2R function on renal inflammation and injury.
Abstract 16705: Abnormal Atrial Substrate Underlies Atrial Fibrillation in Rats With Heart Failure With Preserved Ejection Fraction
Authors: Zhang Rui , Cho Jae Hyung , Goldhaber Joshua I. , Marbán Eduardo , Cingolani Eugenio
Published: April 2024

Introduction:
Atrial fibrillation (AF) is common in patients with heart failure with preserved ejection fraction (HFpEF), and heralds a poor prognosis, but the underlying mechanisms are not well studied.

Hypothesis:
We tested the hypothesis that prolonged atrial effective refractory period (AERP) and slow conduction predispose to AF in HFpEF rats.

Methods:
Dahl salt-sensitive rats were fed a high-salt diet from 7 weeks of age to induce HFpEF (n=32). Normal-salt fed rats were used as controls (n=26). Echocardiograms at 14-15 weeks of age were used to verify diastolic dysfunction and to assess left atrial size. Electrical phenotype was probed by electrocardiography (P wave duration, PR interval) and
in vivo
provocative electrophysiological testing (using a 1.5 French catheter) in echo-verified HFpEF and control rats. Optical mapping was performed to measure action potential duration (APD) and conduction velocity (CV) in
ex vivo
HFpEF and control hearts.

Results:
High-salt fed rats showed decreased E/E’ ratio with preserved ejection fraction (60-70%), hence were diagnosed with HFpEF. Left atrial size was increased in rats with HFpEF compared to controls (29.1±0.8 vs. 19.5±1.1 mm
2
, p<0.001). P waves were prolonged in HFpEF rats compared to controls (17.8±0.5 vs. 13.5±0.6 ms, p<0.001), as was the PR interval (57.8±1.1 vs. 48.8±1.3 ms, p<0.001). AF induction after burst pacing was much easier in HFpEF rats (27/32 HFpEF rats compared to 5/26 controls, 84.4 vs. 19.2%, p<0.001). Atrial effective refractory period (AERP) was prolonged in HFpEF rats compared to controls (37.8±1.7 vs. 30.6±1.8 ms, p<0.01). During optical mapping, APD was prolonged in left atrium of HFpEF rats compared to controls (APD90 42.3±3.6 vs. 30.9±2.2 ms, p<0.05), atrial CV was slower in HFpEF rats compared to controls (0.31±0.03 vs. 0.46±0.02 mm/ms, p<0.01).

Conclusions:
Rats with HFpEF were at increased risk of inducible AF after burst pacing. Decreased atrial conduction velocity and prolonged AERP contribute to the pathogenesis of AF in HFpEF.
Abstract 16707: Human Embryonic Stem Cell-Derived Cardiomyocytes Are Safe and Improve Infarct Size and Cardiac Function in a Porcine Model of Myocardial Infarction
Authors: Banerjee Monisha N , Bagno Luiza , Florea Victoria , Rieger Angela C , Mitrani Raul , Rodriguez Jose , Rosado Marcos , Sanchez Jennifer , Desai Sohil S , Alvarez Alexandra L , Chase Ren , Khan Aisha , Balkan Wayne , Neofytou Evgenios , Wu Joseph C , Hare Joshua M
Published: April 2024

Introduction:
Stem cell therapy is an emerging means of stimulating cardiac repair after myocardial infarction (MI). Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) are a novel therapeutic option, with the potential for cell derived remuscularization. This study assessed the safety and efficacy of these cells, is the first to test these cells in a porcine model of MI, and used electrophysiologic (EPS) testing to evaluate potential arrhythmogenicity.

Methods:
Yucatan swine underwent a left anterior descending coronary artery ischemia/reperfusion protocol to form an MI. Four weeks later, either placebo (n=3) or 3 x 10
8
hESC-CMs were delivered via transendocardial stem cell injection (TESI) (n=4). All animals received immunosuppression for 2 weeks following TESI. Three uninfarcted animals received cells. Cardiac function and LV chamber volumes were measured using pressure volume catheterization and cardiac MRI at 4, 8 and 12 weeks post-TESI. Inducibility of ventricular tachycardia (VT) was tested at 4 and 12 weeks post-TESI by programmed ventricular stimulation via a catheter in the RV apex. Histology of heart tissue and organs was evaluated.

Results:
Twelve weeks post-TESI, scar size (scar mass as a % of total LV mass) was reduced in the cell treated group by -2.33±0.03% (p=0.034), a 12.69±1.87% reduction from pre-TESI. Scar size remained constant in the placebo group. The rise in end diastolic volume at 12 weeks in the placebo group (15.6±7.35 mL; p=0.032) was attenuated in the cell treated group (10.39±6.36mL; p=0.17). By 12 weeks post-TESI, Ees (slope of ESPVR) increased by 0.51±0.15 mmHg/mL (p=0.045) and in the cell treated group but was unchanged in placebo (-0.09±0.85 mmHg/mL; p= 0.92). Following TESI, only 1 animal from each group had inducible VT. No animals had spontaneous VT as measured by an implantable loop recorder. Cardiac function and structure of uninfarcted animals did not change over the study, and none of these animals had inducible VT. Histology did not reveal ectopic tissue formation or signs of rejection.

Conclusion:
TESI of hESC in a porcine MI model is safe, does not increase the risk of either spontaneous or inducible arrhythmias compared to placebo, reduces scar size and remodeling and improves cardiac contractility as measured by Ees. Translation to clinical studies is warranted.
Abstract 16719: Vascular Endothelial Growth Factor-C and Mortality in Patients With Stable Coronary Artery Disease and Cancer: A Subanalysis of the ANOX Study
Authors: Iguchi Moritake , Suzuki Masahiro , Matsuda Morihiro , Ajiro Yoichi , Shinozaki Tsuyoshi , Sakagami Satoru , Yonezawa Kazuya , Shimizu Masatoshi , Funada Junichi , Takenaka Takashi , Morita Yukiko , Nakamura Toshihiro , Fujimoto Kazuteru , Matsubara Hiromi , Kato Toru , Unoki Takashi , Takagi Daisuke , Ura Shuichi , Wada Kyoma , Masunaga Nobutoyo , Ishii Mitsuru , Yamakage Hajime , Shimatsu Akira , Kotani Kazuhiko , Satoh-Asahara Noriko , Abe Mitsuru , Akao Masaharu , Hasegawa Koji , Wada Hiromichi
Published: April 2024

Background:
Recent basic studies suggest the importance of lymphatic vasculature as a therapeutic target in cardiovascular diseases, whereas clinical investigations of vascular endothelial growth factor-C (VEGF-C), a central player in lymphangiogenesis, have focused on its diagnostic possibilities for various malignancies. The expression levels in tumors and/or circulating levels of VEGF-C correlates with lymph node and distant metastasis, and poor prognosis. However, the relationship between VEGF-C and mortality in patients with stable coronary artery disease (CAD) and cancer is unknown.

Methods:
Serum VEGF-C levels were measured in 133 patients with stable CAD and cancer, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict cardiovascular events (ANOX) study, and followed up for 3 years. The outcome was all-cause death.

Results:
During the follow-up, 43 patients (32%) died from any cause (10 patients from cardiovascular cause, and 25 patients from cancer). In Kaplan-Meier analysis, lowest quartile of VEGF-C was significantly associated with all-cause death (hazard ratio [HR], 2.6; 95% confidence interval [CI], 1.4-4.8, but not with cancer-related death (HR, 1.8; 95% CI, 0.8-4.2). After adjustment for established risk factors, low VEGF-C levels and the lowest quartile of VEGF-C were both significantly associated with all-cause death (HR for 1-SD increase, 0.67; 95% CI, 0.47-0.95; HR for values below the 25th percentile, 3.3; 95% CI, 1.7-6.3; respectively). Even after additional adjustment of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein, low VEGF-C levels and the lowest quartile of VEGF-C were both significantly associated with all-cause death (HR for 1-SD increase, 0.69; 95% CI, 0.48-0.99; HR for values below the 25th percentile, 2,7; 95% CI, 1.4-5.5; respectively).

Conclusions:
In patients with stable CAD and cancer, a low VEGF-C value was independently associated with all-cause mortality beyond established risk factors and standard cardiovascular biomarkers. These findings may indicate the difficulty to use elevated VEGF-C as a prognostic marker in patients with cancer.
Abstract 16720: Exercise-Stimulated Catecholamine Release Enhances Resolution of Acute Inflammation
Authors: Zheng Jing-Juan , Pena Calderin Ernesto , Hill Bradford G , Bhatnagar Aruni , Hellmann Jason
Published: April 2024

The mechanisms by which regular exercise prevents the development and progression of chronic inflammatory diseases are largely unknown. We find that exercise (Exe) enhances resolution of acute inflammation by promoting macrophage (MФ) phagocytosis and by augmenting resolvin D1 (RvD1) levels. When compared with sedentary controls (Sed), mice adapted to a 4-week treadmill exercise regimen displayed 1.48-fold higher MФ phagocytotic activity, enhanced RvD1 levels (Sed 28.08±1.5 vs Exe 48.01±8.6 pg/mL, n=6), and earlier neutrophilic clearance (ΔR
i
~7 h) during peritonitis. Peritonitis cell extracts from exercise-adapted mice showed elevated expression of
Alox15
(48 h: Sed 0.97±0.15 vs Exe 1.5±0.16 relative expression, n=8-9),
Alox5
(48 h: Sed 0.77±0.15 vs Exe 1.7±0.27 relative expression, n=4-5), and RvD1 levels (48 h: 29.0±2.1 vs 52.6±8.9 pg/mL, n=5). Because exercise stimulates epinephrine (Epi) release, which has immunomodulatory effects, we questioned if Epi exerts pro-resolving actions on macrophages. Epi-treated macrophages displayed higher 15-lipoxygenase 1 expression and RvD1 levels, which were prevented by incubation with the α1 adrenergic receptor (AR-α1) blocker, Prazosin (Praz). During zymosan-induced peritonitis, Praz abrogated exercise-enhanced neutrophilic clearance (48 h: Exe+Veh 2.07±0.41 vs Exe+Praz 5.2±1.04 x10
6
PMN, n=5), MФ phagocytosis (Exe+Veh 33463.0±2174.0 vs Exe+Praz 8303.0±2748.0 MFI, n=5-7), and RvD1 biosynthesis (Exe+Veh 211.0±55.4 vs Exe+Praz 81.79±11.8 pg/mL, n=6). These results suggest that exercise-stimulated Epi release enhances resolution of acute inflammation in an AR-α1 dependent manner. These findings provide new mechanistic insights into the pro-resolving effects of exercise and may lead to the identification of novel pathways to stimulate resolution biology.
Abstract 16736: Etiology of Sudden Cardiac Arrest in Young Primary and Referral Populations: The Mayo Clinic Experience
Authors: Rodriguez-Cartagena Luis G , Bos J. Martijn , Giudicessi John R , Ackerman Michael J
Published: April 2024

Introduction:
The incidence and etiologies underlying sudden cardiac arrest (SCA) in the young are derived from population- and referral-based cohorts of young SCA survivors. The extent to which the use of these cohorts contributes to discrepancies in our understanding of SCA in the young is unknown. As such, we sought to determine and compare the spectrum of SCA etiologies observed in young SCA survivors evaluated at a single tertiary center on both a primary and referral basis.

Methods:
Retrospective review of 940 young SCA survivors evaluated between 1990 and 2017 was used to identify all individuals ≤ 50 years of age that experienced a SCA. SCA root cause was determined by review of the medical records and diagnoses classified as ischemic, primary electrical, structural, or unexplained. SCA survivors that initially presented to our institution were classified as primary, while those who presented for secondary evaluation received a referral classification.

Results:
Overall, 566 SCA survivors were identified (age at event 33 ± 14 years; 39% females). In comparison to primary SCA survivors, referral SCA survivors were younger at the time of SCA (39 ± 12 vs. 30 ± 14 years; p<0.0001) and less likely to experience pre-SCA symptoms (45% vs. 27%; p<0.0001). Among all SCA survivors, the most common etiologies were idiopathic ventricular fibrillation (27%), acute coronary syndrome (21%), long QT syndrome (10%), and hypertrophic (7%) and dilated (6%) cardiomyopathies. Ischemic etiologies were less common (45% vs. 25%; p<0.0001) and primary electrical disorders more common (6% vs. 23%; p<0.0001) in referral SCA survivors. Conversely, genetic heart diseases (hypertrophic cardiomyopathy, long QT syndrome, etc.) were over-represented in referral cases (8% vs. 29%; p<0.0001), whereas no difference was observed in the number of primary and referral SCAs that remained unexplained.

Conclusion:
This study demonstrates, for the first time, that differences in SCA root cause exist between young SCA survivors evaluated at the same tertiary medical center on a primary vs. referral basis. Ongoing comparison of SCA etiologies between primary and referral SCA survivors may help resolve discrepancies regarding the contribution of specific disorders to SCA in the young.
Abstract 16738: Reendothelization of a Pediatric-Sized Decellularized Heart Using Cells Grown in a Closed Expansion System
Authors: Hochman-Mendez Camila T , Mesquita Fernanda C , Morrissey Jacquelynn T , Tang-Quan Karis R , Xi Yutao T , Feng-Lee Po T , Sampaio Luiz C , Taylor Doris A
Published: April 2024

Background:
Coagulation is a significant issue in bioengineering of vascularized tissues. Reendothelization is a strategy commonly used to prevent it in bioartificial organs. However, the large number of cells required for full coverage of blood vessels in a human-sized heart is a bottleneck in this field. Closed cell expansion systems (e.g., Quantum Cell Expansion System, QES) may provide a solution to this issue. The goal of this work was to reendothelize a pediatric-sized decellularized heart using human induced pluripotent stem cell-derived endothelial cells (hiPSC-dEC).

Methods:
hiPSC-dEC were expanded using the QES and cultivated with decellularized cardiac patches or perfused into whole decellularized rabbit hearts. Reendothelized cardiac patches and whole hearts were evaluated by live/dead staining, histology, scanning electron microscopy (SEM) and immunofluorescence.

Results:
Our results demonstrated that QES induced exponential iPSC-dEC growth, producing 36.14x10e7 ± 2.34x10e7 cells after 5-9 days (n=13). After cell expansion, these cells expressed von Willebrand Factor (vWF) and CD31, maintaining the phenotype of the endothelial cells. They also retained the capacity of cell-cell interaction evaluated by VE-cadherin staining. Rabbit hearts (8 ± 1.3 grams) were decellularized by whole organ perfusion. Decellularized hearts were grossed to produce cardiac patches (n=9) or were recannulated in a customized closed apparatus with controlled temperature and gas exchange for recellularization (for whole organ recellularization, n=6). Expanded hiPSC-dECs were attached (74.9 ± 2.9%) to cardiac patches, forming vessel-like structures, surviving for at least 17 days in the patches. These patch studies were used to extrapolate the number of cells, the frequency of medium exchange and cell attachment and orientation needed for decellularized hearts. Based on these data, one hundred million hiPSC-dEC were perfused into the whole decellularized rabbit heart through the coronary trees and cultivated for 7 days. Recellularized hearts showed that cells selectively attached to the small and large vessels and the endocardium but were not observed outside of vessels.

Conclusion:
Together, these findings demonstrate that hiPSC-dEC expanded in a system can repopulate pediatric-size hearts by covering vessel walls and thus provide a favorable environment to prevent coagulation after transplantation.
Abstract 16756: Coxsackievirus Infection During Early Pregnancy Leads to Congenital Heart Defects
Authors: Sharma Vipul , Goessling Lisa , Brar Anoop , Eghtesady Pirooz
Published: April 2024

Introduction:
Coxsackievirus B (CVB), the most common cause of myocarditis, targets cardiomyocytes through the Coxsackie and Adenovirus Receptor which is highly expressed in the fetal heart. Association between maternal CVB infection and fetal cardiac malformations has not been studied.

Hypothesis:
CVB infection during early pregnancy may play a role in the pathogenesis of congenital heart disease (CHD).

Methods:
Pregnant C57Bl/6J mice were infected between embryonic days (E) 5-11 with CVB3 (Nancy strain) at doses 1x10
6
, 2.5x10
6
, and 5x10
6
TCID50. Presence of the virus was confirmed by RT-PCR and infectivity assay and quantified by qPCR. Fetal heart phenotype was assessed by histology and to determine changes at the molecular level after infection, RNA was collected from fetal hearts using laser microdissection and analyzed by RNA-Seq. The results were confirmed by immunohistochemistry and qPCR. To assess the potential clinical relevance of our observations in mice, we analyzed the sera from pregnant women for presence of antibody titers against of CVB.

Results:
Offspring of pregnant mice infected with CVB3 at different time points developed a spectrum of CHD (38.2%, n=78/204): ventricular septal defect, double outlet right ventricle, and non-compaction of the ventricular myocardium, along with fetal death. Infection at E9 led to the highest incidence of VSD compared to infection earlier (E5, E7 or E8) or later (E11) in gestation. Transcripts found to be differentially expressed between infected fetal hearts with VSDs compared with controls were mediators of the Transforming growth factor β and Extracellular matrix signaling pathways. Consistent with the former, expression levels of BMP2 and Smad1/5/9 mRNA were elevated. Simultaneously suppressed proliferation of cardiomyocytes in these fetuses was observed. Serum analysis from 66 pregnant women who had babies with heart defects showed elevated titers of antibodies against CVB underlining the clinical significance of CVB infection during pregnancy.

Conclusions:
In mice, there is a critical window during pregnancy where CVB infection leads to abnormal cardiac development, likely through reduction of cardiomyocyte proliferation mediated by elevated levels of BMP2 and Smad1/5/9. Collectively, the data confirm a link between CVB infection and CHD development in mouse and human.
Abstract 16759: Repair of Functional Mitral Regurgitation Restores Life Expectancy in Selected Patients Less Than 70 Years of Age
Authors: Chan Vincent , Messika-Zeitoun David , Ruel Marc , Glineur David , Elmistekawy Elsayed , Mesana Thierry
Published: April 2024

Introduction:
Functional mitral regurgitation (MR) is common and associated with significant morbidity and mortality. Notably, correction of functional MR has not been demonstrated to improve survival. We therefore evaluated outcomes following repair of functional MR utilizing prospective population data.

Hypothesis:
We hypothesized that correction of functional MR may be associated with a survival benefit in selected patients.

Methods:
Between 2001 and 2018, 1896 patients underwent complex mitral surgery at our institution, of which 168 underwent repair of functional MR in whom the etiology of MR was due to annular dilation in 37, leaflet tethering in 100 and mixed in 31. Mean patient age was 66.2±9.9 years and 66 (39%) were female. Concomitant coronary artery bypass grafting was performed in 79 (47%) with an average of 2.5 grafts per patient. The mean preoperative left ventricle (LV) ejection fraction was 38.3±11.4% and indexed LV end-systolic dimension, 25.1±5.4 mm/m
2
. Average clinical and echocardiographic follow up averaged 5.5±3.8 years.

Results:
Thirty-day mortality was 0.6%. Overall survival for the patients following repair of functional MR was 93.3±2.0% and 75.6±3.8% 1-, and 5-years after surgery. Not surprisingly, sensitivity analysis demonstrated that survival was influenced by age at operation (hazard ratio (HR) 1.05±0.02 per increasing year) and preoperative left ventricle (LV) class (HR 1.32±0.18 per increasing LV grade) (Both p<0.05). For patients <70 years of age and with a preoperative LVEF >35%, 5- year survival was 92.3±7.4%, respectively. This compares to an expected 5- year survival of 99.1%, for age and gender matched Canadians (Figure). For patients <70 and with a preoperative LVEF >35%, 5-year freedom from recurrent MR ≥2+ was 81.3±9.8%.

Conclusions:
Repair of functional MR is associated with favorable early and intermediate term results in selected patients. Notably, for the subset of functional MR patients <70 and with a LVEF>35%, 5-year survival was comparable to age and gender matched patients from the general population.
Abstract 16766: Increased Clinical and Financial Burden of Heart Failure Hospitalizations in Patients With Systemic Lupus Erythematosus: Insights From the National Inpatient Sample 2012-2014
Authors: Joshi Aditya A , Sajja Aparna P , Dey Amit K , Lerman Joseph B , Aberra Tsion M , Patorroyo-Aponte Maria M , Murali Srinivas , Benza Raymond L , Raina Amresh
Published: April 2024

Introduction:
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease associated with increased cardiovascular (CV) co-morbidities. Recent evidence suggests that (SLE) is associated with higher incidence of heart failure (HF) independent of traditional CV risk factors. Despite a known association with accelerated CV diseases, the association between burden of acute decompensated HF (ADHF) and SLE is not well-characterized. Therefore, we used a large national database to examine the clinical and financial burden of ADHF in SLE.

Hypothesis:
SLE would associate with increased hospitalization for ADHF along with a longer length of stay (LOS) and higher hospital charges.

Methods:
SLE patients (n=160,350) older than 18 years were identified in the Nationwide Inpatient Sample (NIS) 2012-2014 databases using the ICD-9 code 710.0. ADHF was classified using appropriate ICD-9 codes from 428.0-428.9. Demographics, traditional CV risk factors, and HF-related outcomes were defined in SLE patients and compared to the general population.

Results:
Patients in the general population and with SLE were middle-aged (median 56 and 59 years). Prevalence of hypertension and chronic kidney disease was higher in SLE patients, whereas diabetes, coronary artery disease, dyslipidemia was lower (Table 1). ADHF rate, LOS and total hospital charges were increased in SLE. Furthermore, LOS (standardized β=0.003, p<0.001) and hospital charges (β=0.006, p<0.001) were associated with SLE beyond CV risk factors. Finally, after adjustment for CV risk factors (age, sex, hypertension, diabetes, dyslipidemia, coronary artery disease, chronic kidney disease, smoking), dysrhythmias, thyroid disorders, alcohol use and median household income, SLE associated with ADHF (OR, 95% CI: 1.53 [1.51-1.55], p<0.001), increased LOS (1.14 [1.11-1.17], p<0.001) and increased hospital charges (1.12 [1.09-1.15], p<0.001) (Table 1).

Conclusion:
SLE is associated with increased clinical and financial burden of ADHF beyond CVRF, underscoring the need for greater early clinical awareness of SLE in HF patients. Larger prospective studies are needed to confirm our findings.
Abstract 16779: Mitochondrial Related Intragraft Gene Expression During Acute Rejection After Heart Transplantation
Authors: Romero Erick S , Chang Eleanor , Villarente Laurel , Fishbein Gregory A , Cadeiras Martin
Published: April 2024

Introduction:
Endomyocardial biopsies (EMB) for the surveillance of acute cellular rejection (ACR) after heart transplant (HT) is inconsistent and provides limited information. Mitochondrial dysfunction is associated with poor allograft prognosis and can overstimulate the inflammatory response. Mitochondrial related gene expression (GE) in EMB may be useful as a functional surrogate for EMB.

Hypothesis:
We hypothesize that down-regulated mitochondrial associated GE in EMB correlates with ACR.

Methods:
We collected 64 EMB from 47 post HT patients (mean age 50 ± 14.7 years). Purified mRNA was subjected to whole-genome next-generation sequencing. Weighted gene co-expression network analysis was applied to construct functional gene modules. Module derived eigengenes were correlated with ISHLT EMB criteria or using an unsupervised classification method we previously developed and B-type natriuretic peptide (BNP) levels. Biological significance and function of each module were assessed by gene ontology (GO) and pathway analyses. Highly relevant genes were identified by Hub gene analysis.

Results:
The reconstructed network resulted in 16 modules including two mitochondria-related modules (MRM) and one immune response module (IRM). Compared to 0R (n= 30/46.9%) samples, 2R (n= 11/17.2%) EMB showed enrichment of IRM and decreased expression of MRM. ISHLT 1R (n= 23/35.9%) samples did not show a significant correlation with IRM or MRM. Following the unsupervised classification method, findings were concordant, with higher phenotype-module eigengene correlation and significance level. MRM Hub genes included
ATP5B, ATP5O, ACO2, COX14, COX4I1
,
FH, NDUFV1, PDK2, SDHA
and
UQCR11
among others. GO categories enriched by these genes included oxidative phosphorylation, beta-oxidation, tricarboxylic acid cycle, glycolysis and gluconeogenesis. There was an inverse correlation between MRM and BNP level and positive correlation between IRM and BNP (Figure).

Conclusions:
EMB of patients with ISHLT 2R ACR show decrease activity of MRM, increased activity of IRM and elevated BNP suggesting an inverse functional relationship between immune activation, mitochondrial activity and cardiac allograft function.
Abstract 16788: Anatomical Repair Can Be Facilitated by Three-Dimensional Cardiac Printing in the Patients With Double Outlet Right Ventricle
Authors: Kim Dong-Hee , Choi Eun Seok , Park Chun Soo , Yun Tae-Jin
Published: April 2024

Introduction:
Determination of optimal strategy between single ventricle palliation (SVP) versus left ventricular recruitment (LVR) as a systemic ventricle is challenging in the patients with complicated double outlet right ventricle (DORV). We sought that three-dimensionally printed cardiac models (3DM) may enables the surgeons to make an intuitive preoperative decision potentially in favor of LVR.

Hypothesis:
Use of 3DM can extend the candidates for LVR and improve surgical outcomes.

Methods:
We retrospectively reviewed the patients with DORV from Jan 2008 to Jun 2018 in single center. The patients with discordant atrioventricular (AV) connection, complete AV septal defect and atresia of AV valves were excluded. The patients without at least one of LVR precluding factors such as left or right ventricular hypoplasia, mitral valve (MV) or tricuspid valve (TV) straddling, TV interposition in potential baffle course, huge ventricular septal defect (VSD), multiple VSDs and remote VSD were excluded. All patients were divided in SVP or LVR group except two patients without clear determination of strategy. Finally, 100 patients were enrolled and since 2016, 3DM was made in the patients with LVR precluding anatomy for better consensus formation whether LVR could be feasible in 26 patients. Risk factor analysis was done for SVP and adverse outcome.

Results:
Thirty-five patients enrolled as SVP strategy (Fontan operation in 14, Kawashima operation in 1, interstage mortality in 12, follow-up loss in 3 and waiting scheduled operation in 5) and 65 patients enrolled as LVR strategy (complete anatomical correction in 50, one and half ventricle repair in 6 and waiting scheduled operation in 9). In multivariate analysis, LV hypoplasia (
P
=0.003) and MV straddling (
P
=0.015) were significant LVR precluding factors and the use of 3DM was a favorable factor for LVR (
P
=0.039, OR=0.212). Risk factor for mortality were LV outflow tract obstruction (
P
=0.006) and LV hypoplasia (
P
=0.043). The use of 3DM did not reach statistical significance on mortality (
P
=0.132).

Conclusions:
In DORV patients, LVR can be precluded especially with LV hypoplasia and MV straddling however, LVR can be facilitated by direct-vision driven preoperative decision about complicated features with 3DM.