bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14916: Computerized Working Memory Training for Hypertensive Individuals With Executive Function Impairment: A Randomized Clinical Trial
Authors: Paradela Regina S , Cabella Brenno , Nucci Mariana P , Ferreira Naomi V , Torres Laura A , Martino Luiza M , Consolim-Colombo Fernanda M , da Costa Danielle I , Irigoyen Maria Claudia
Published: June 2023

Introduction:
Hypertension is a risk factor for working memory (WM) impairment, and the Cogmed training has been tested as a non-pharmacological alternative to WM rehabilitation. However, the benefits of Cogmed for the hypertensive population are unknown. Therefore, we aimed to evaluate Cogmed’s effects on WM performance of hypertensive individuals with executive function (EF) impairment.

Methods:
We included 40 hypertensive patients (aged 40 to 70 years, 68% female) with EF impairment. They were randomized in a 1:1 ratio to receive ten weeks of adaptive Cogmed training or a non-adaptive control training based on online games. The primary outcome was the WM performance. The secondary outcomes were the performance in other neuropsychological tests, as well as the indirect neuronal activity measured using functional magnetic resonance imaging (fMRI) under two WM task conditions: low (memorization of 4 spatial locations) and high (memorization of 6 spatial locations). An intention-to-treat (ITT) and per-protocol (PP) analysis were performed. The fMRI images were evaluated with the FSL tools. Cognitive outcomes were analyzed with a mixed model for repeated measures.

Results:
Compared to the control group, the Cogmed group did not show significant improvement in WM or any other cognitive outcome post-training (ITT and PP analysis). However, under the WM-low load and WM-high load conditions, respectively, the Cogmed group had an activation decrease in the right superior parietal lobe (ITT and PP analysis) and left inferior frontal lobe (PP analysis) in comparison to the control group (p<0.05).

Conclusions:
The Cogmed showed no effects on WM performance of hypertensive individuals with EF impairment. However, activation decreases were observed in frontoparietal areas related to the WM network, suggesting intervention-related increases in neural efficiency.
Abstract 14920: Differences in Socioeconomic Factors in Patients Obtaining Coronary Calcium Score Computed Tomography in a Large Midwestern Healthcare Network
Authors: Chapel Andrew , Zlochiver Viviana , Adefisoye James , Garg Kritika , Reddy Alexander , Peterson Michael , Plautz Doreen , Kram Jessica , Port Steven , Galazka Patrycja
Published: June 2023

Introduction:
Coronary artery calcium score (CACS) is an important tool for identifying subclinical atherosclerosis and cardiovascular risk stratification. The 2018 ACC/AHA Cholesterol Guideline includes CACS as a decision aid in asymptomatic, intermediate-risk patients. In most US states, including Wisconsin, CACS is not covered by insurance with out-of-pocket costs ranging from $50-400. This study aimed to examine the socioeconomic factors of Wisconsin patients who obtained a CACS CT at Advocate Aurora Health (AAH).

Methods:
Using the 2018 American Community Survey data from the Census Bureau, we evaluated the socioeconomic characteristics of the areas in Wisconsin where patients who underwent CACS CT at AAH lived. These included race, ethnicity, median income, median age, average household size, household without vehicles, and completion of high school. We categorized the income as low (≤$35,000), medium (>$35,000 - <$100,000), and high (≥$100,000). Additionally, we compared self-referred versus physician-referred patient characteristics.

Results:
A total of 19,726 patients presented for CACS CT at AAH from 2019 through 2021. The median income for patient residential areas was $73,981. The median percentage of white race in these areas was 94.6%, while that of black race was only 0.3%. Additionally, median percentage of Hispanics was 2.9%. The median average household size was 2.5 people, median percentage of households who did not own a vehicle was 2.2%, and the median high school completion rate was 95.2%. When we stratified by income, most patients were from areas with medium income (75.2%), followed by high (17.3%), and only 7.5% were from low-income areas. When comparing self-referred versus physician-referred patients, self-referred were found to live in higher-income areas compared to physicians-referred (19.4% vs. 16.4%; p<0.0001).

Conclusion:
Social and economic factors are well known to affect access to health care. Our study demonstrated that patients in Wisconsin who obtain out-of-pocket CACS CT live predominantly in medium and high-income areas. Patient access to preventive health care may be affected by the lack of insurance coverage.
Abstract 14923: A Special Type Aortic Left Ventricular Tunnel With Bicuspid Aortic Valve: A Case Report
Authors: Song Yi , An Jindou , Liu Huiruo
Published: June 2023

Introduction:
Aortic-left ventricular tunnel (ALVT) is an extremely rare congenital cardiac lesion that is an abnormal passage connecting the ascending aorta to the left ventricle. ALVT can be diagnosed by the use of real-time two-dimensional and continuous-wave Doppler echocardiography.
Case presentation:
A two-year and seven-month-old boy with recently diagnosed influenza presented to the hospital because of severe tachypnea and fatigue after running. Physical examination revealed a grade 3/6 systolic and diastolic murmur at the second and third left intercostal space. Transthoracic echocardiography (GE E95 with a 5-MHz scanning head) demonstrated that the aortic valve was a bicuspid aortic valve (BAV) with mild-moderate insufficiency during diastole, the peak systolic velocity (PSV) and gradient of aortic valve were 1.9m/s and 14mmHg, respectively; The aortic sinotubular junction (ASJ) was stenotic, the PSV and gradient of ASJ were 2.7m/s and 29mmHg, respectively; A tubular-like structure originated in the outlet septum beneath the right coronary cusp and terminated in the ascending aorta superior to the right coronary aortic sinus (Fig. A, B), CDFI and continuous-wave Doppler showed unobstructed to-and-fro (systolic and diastolic) flow in the tunnel with a high-velocity color signal that aliased during systole (Fig. C-E). Clinical considerations for congenital heart disease: ALVT combines BAV with aortic insufficiency and supravalvar aortic stenosis. The patient was referred for possible surgical correction.

Discussion:
In this patient, the type of ALVT does not belong to any one of Hovaguimian’s classifications. Two-dimensional echocardiography can display the tunnel-like structure of ALVT in real-time, and CDFI can identify that two-stage bidirectional shunted blood flow, systolic ventricular ejection occurs through both the tunnel and the semilunar valve, and the diastolic flow reverses from the aorta to ventricle via ALVT.
Abstract 14941: Association of WATCH-DM Risk Score With Cardiac Abnormalities and Prevalence of Diabetic Cardiomyopathy: A Prospective Cohort Study
Authors: Chunawala Zainali , Raygor Viraj , Segar Matthew , Chandra Alvin , Pandey Ambarish
Published: June 2023

Introduction:
Diabetic cardiomyopathy (DbCM) is characterized by abnormal cardiac structure or function in the absence of cardiovascular disease (CVD). We assessed whether WATCH-DM, a validated risk score to predict incident heart failure (HF) in patients with DM, can identify DbCM.

Methods:
We prospectively enrolled 150 individuals with DM free of known CVD or overt HF in a single-center institution. The presence of DbCM was calculated using different definitions: 1) least restrictive: ≥1 echocardiographic abnormality (left atrial enlargement, left ventricular hypertrophy, diastolic dysfunction); 2) intermediate restrictive: ≥2 echocardiographic abnormalities; and 3) most restrictive: elevated N-terminal pro-B-type natriuretic peptide levels (>125 in normal/overweight or >100 pg/mL in obese) plus ≥2 echocardiographic abnormalities. DbCM prevalence was compared across high (scores ≥ 11) and low (scores < 11) WATCH-DM using chi-squared test. Adjusted logistic regression models were used to evaluate the association between WATCH-DM and components of DbCM.

Results:
The prevalence of DbCM ranged from 60.7% to 7.3% in the least and most restrictive definitions, respectively. Subjects with high (vs. low) WATCH-DM score were more often males (58% vs 32%), older (71 vs 68 years) and had a longer duration of DM (13 vs 10 years). Moreover, the concentration of NT pro-BNP was observed to be significantly higher in the high WATCH-DM cohort. Across definitions, individuals with high WATCH-DM had a numerically higher prevalence of DbCM (
Fig. A
). Among individual components, high WATCH-DM was associated with a higher risk of diastolic dysfunction (OR [95% CI] = 2.53 [1.20-5.54]) (
Fig. B
). We observed no significant differences in LV hypertrophy or LA enlargement across WATCH-DM scores.

Conclusion:
High WATCH-DM risk score is associated with a higher prevalence of DbCM and echocardiographic abnormalities and may be an effective tool for identifying patients with DbCM.
Abstract 14944: Comorbid Obesity in Symptomatic Peripheral Artery Disease: A Modifiable Factor Associated With Health Status
Authors: Scierka Lindsey , peri-Okonny poghni A , Mena-Hurtado Carlos , Gosch Kensey , Spertus John , Fitridge Robert , Vriens Patrick W , Soedamah-Muthu Sabita , Smolderen Kim G
Published: June 2023

Introduction:
Obesity is a modifiable risk factor for peripheral artery disease (PAD). While highly prevalent, the association between obesity and health status outcomes in PAD has not been studied. We aim to summarize obesity management and its association with health status in patients with PAD.

Methods:
We conducted a longitudinal cohort study of patients with symptomatic PAD from the international multicenter PORTRAIT registry. Body mass index (BMI) was analyzed continuously (per 10kg/m2) and categorically as underweight (BMI < 18.5 kg/m
2
), normal weight (BMI 18.5 - 24.9 kg/m
2
), overweight (BMI 25 - 29.9 kg/m
2
) and obesity (BMI > 30 kg/m
2
). Obesity management strategies included diet or weight counseling and anti-obesity medications. Disease-specific health status was assessed with the Peripheral Artery Questionnaire (PAQ) (range=0-100, higher scores indicate better health status). Linear regression models examined the association between obesity and both baseline and 12-month PAQ summary scores.

Results:
Obesity was present in 37% (370/989) of patients (mean age 68.0
+
9.1 years, 40.1% female). No patients received anti-obesity medications. Weight and/or diet counseling were prescribed in only 12% of overweight and in 21% of patients with obesity. BMI (per 10 kg/m
2
) was associated with worse PAQ summary scores at baseline (-5.7, 95% CI -8.0 to -3.5,
p
<0.01) and 12 months (-7.8, 95% CI -12.3 to -3.4,
p
<0.01) in unadjusted and models adjusting for medical comorbidities and PAD-associated factors. This was consistent when obesity was compared categorically to normal/overweight at baseline (mean difference = -7.2, 95% CI -10.4 to -4.1,
p<
0.01) and at 12 months (-7.4, 95% CI -11.4 to -3.5,
p<
0.01).

Conclusions:
Obesity is a potentially modifiable comorbidity in PAD that is currently under addressed and a strong correlate of PAD-specific health status following PAD diagnosis and treatment.
Abstract 14950: Single-Cell Transcriptomic Analysis Reveals Emergence of Inflammatory and Activated Arterial Endothelial Cells Promoted by Cross-Talk With Mural Cells During Development of Severe Pulmonary Arterial Hypertension
Authors: Cober Nicholas D , McCourt Emma , Soares Godoy Rafael , Deng Yupu , Schlosser Ken , Cook David , Wang Liyuan , Stewart Duncan J
Published: June 2023

Introduction:
Pulmonary arterial hypertension (PAH) is a lethal disease characterized by occlusive arterial remodelling thought to be triggered by endothelial cell (EC) injury; however, the pathobiological mechanisms are poorly understood. We employed single cell RNA sequencing (scRNAseq) to define transcriptomic changes in the SU5416/chronic hypoxia (SU/CH) rat model.

Methods:
Sprague-Dawley rats were injected with 20mg/kg SU subcutaneously and exposed to 3 weeks of CH (10% O
2
). Right ventricular systolic pressure (RVSP) was measured at baseline, 1, 3, 5, and 8-weeks, then lungs were explanted, digested, and dissociated into single cells which were sequenced using the 10x genomics platform.

Results:
Elevation of RVSP plateaued at >100 mmHg by 5 weeks. Dimensionality reduction of the scRNAseq data was performed using Uniform Manifold Approximation and Projection (UMAP) analysis resulting in 24 lung clusters. Cell prioritization analysis performed using Augur identified vascular cells as the most affected by SU/CH, including arterial ECs, pericytes, and gCap ECs. After sub-clustering the EC populations, eight distinct clusters were identified representing all expected subtypes (capillary, arterial, venous, and lymphatic). As well, two novel EC clusters were detected. The first showed reduced expression of classical EC genes (
Cdh5
,
Cldn5
) and increased proinflammatory markers (
RT1-Da
,
Cd74
), termed ‘inflammatory’ ECs. The second was an arterial cluster that exhibited reduced expression of
Dll4
and increased
Cxcl12
and
Fn1
, termed ‘activated’ arterial ECs. Both populations emerging at 1-week post SU, persisting throughout PAH progression. While many EC populations showed marked differential gene expression (DGE) at 1 week, the activated arterial cluster was the only cluster showing progression of DGE throughout progression of PAH. Receptor-ligand analysis with NicheNet identified activated arterial ECs as a top receiver cell responding to multiple ligands, including
Bmp4/5
,
Col4a1
, and
Vegfa/c,
which were largely derived from mural fibroblasts.

Conclusion:
Emergence of inflammatory and activated arterial ECs likely contribute to vascular remodelling associated with PAH promoted by cross-talk with lung stromal cells.
Abstract 14954: Mitochondrial C-Src Regulates Impaired Mitochondrial Bioenergetics in Right Ventricles in Pulmonary Hypertension
Authors: Zhang Peng , Vang Alexander , da Silva Goncalves Bos Denielli , Feord Julia , Wang Eric , D’Silva Natalie , Zimmer Alexsandra , Choudhary Gaurav
Published: June 2023

Introduction:
Pulmonary hypertension (PH) has poor prognosis with presence of right ventricular (RV) dysfunction. However, no RV targeted therapies are available. Mitochondrial (Mito) energy deficiency is detrimental on RV function in PH, but the underlying mechanism remains unclear. Tyrosine kinase phosphorylation (P-Tyr) has been a critical regulatory mechanism in mito. While mito localized c-Src is recognized as the major tyrosine kinase, little is known regarding its role in RV in PH.

Hypothesis:
We hypothesized that mito c-Src regulates impaired mito bioenergetics in RV in PH.

Methods:
PH was induced in adult Sprague-Dawley (SD) rats by injecting 20 mg/kg SU5416, followed by 3 wks of hypoxia (10% FiO
2
) and then 4 wks of normoxia exposure. Control rats injected with vehicle were kept in normoxia. After echocardiography and hemodynamics, RV tissues were collected for mito respiration using high resolution O2K-FluoRespirometer, mito morphology using electron microscopy, and biochemical assays. Cardiomyocytes and H9c2 cells were used for
in vitro
mechanistic studies.

Results:
Compared to controls, PH rats show increased RV systolic pressure and RV dysfunction. Mito complex I-coupled oxidative phosphorylation and electron transfer capacity are significantly reduced in RV of PH rats (O
2
flux per mass: 216±21 vs. 90±19 and 209±22 vs. 91±22 pmol·s-1·mg-1, respectively,
p
<0.01, n=6 each), which is associated with decreased ATP but no changes in mito membrane integrity, mito DNA content, or mito size. Mito c-Src kinase activity and expression are significantly reduced in RV of PH rats and in dysfunctional RV of human patients. Chemical or molecular inhibition of mito c-Src results in a similar reduction of mito respiration in culture as found in RV of PH rats and is associated with decreased ATP production. Mito c-Src phosphorylates NADH dehydrogenase [ubiquinone] flavoprotein 2 (NDUFV2), a critical protein for complex I, and P-Tyr of NDUFV2 is reduced in RV of PH rats.

Conclusions:
Impaired mito bioenergetics is associated with progression of RV dysfunction. Basal mito c-Src kinase activity is required for mito bioenergetics and mito c-Src-dependent P-Tyr of NDUFV2 may serve as a regulatory mechanism in impaired RV mito bioenergetics in settings of PH.
Abstract 14956: Extensive Cardiac Involvement in Laminopathies Diagnosed in Pediatric-Aged Patients: A Single Center Study
Authors: Hayes Emily A , Wright Lydia K , Gajarski Robert , Hor Kan N , Cripe Linda , Kertesz Naomi J , Nandi Deipanjan
Published: June 2023

Introduction:
Lamin A/C (
LMNA
) gene mutations result in a heterogeneous group of inherited conditions termed laminopathies. Cardiac manifestations of laminopathies include atrial and ventricular arrhythmias, atrioventricular conduction disorders, and cardiomyopathy, with or without skeletal muscle involvement. Because this disease is rare and typically presents in adulthood, pediatric data is limited.

Methods:
We identified patients
<
18 years with genetically confirmed mutations in
LMNA
followed at our center between 2003 and 2021. Clinical phenotypes along with cardiac test results were retrospectively catalogued.

Results:
We identified 12 patients with a median age of 5 years at diagnosis (IQR 4-11 years) with a
LMNA
mutation. Nine (75%) patients were male and 10 (83%) had associated skeletal muscle involvement. Of the 12 patients, 10 (83%) developed cardiac manifestations over a median follow up period of 111 months (IQR 91-116 months). Seven patients (58%) had documented arrhythmias (AV block, ventricular/atrial tachycardias) and 3 (25%) underwent pacemaker and/or implantable cardiac defibrillator placement. Three (25%) patients were diagnosed with cardiomyopathy with 1 (8%) requiring a ventricular assist device and 1 (8%) requiring continuous intravenous inotropes and subsequent transplant. Three (25%) patients died during the study period, one awaiting transplant, one from complications post-transplant, and one from non-cardiac causes.

Conclusions:
Cardiac involvement, specifically cardiomyopathy and progressive conduction system abnormalities, were common in pediatric patients with
LMNA
mutations. Early genetic diagnosis of laminopathies followed by frequent surveillance for dysrhythmia and dysfunction is necessary for more timely initiation of advanced cardiac therapies to prevent adverse events. More comprehensive phenotype-genotype correlation is strongly needed.
Abstract 14969: Transcriptome Signature of Cardiac Fibroblasts in HCM Patients Identifies Novel Drivers Of ECM Remodeling and Pro-Inflammatory Signaling
Authors: Ibrahim Ayman M , Galal Aya , Halawa Sarah , Elfawy Hasnaa , Elshorbagy Sara , Roshdy Mohamed , Mohamed Fiesal , Osman Manar , Hosny Mohamed , Khedr Hadir , Moustafa Ahmed , allouba mona , Aguib Yasmine , Yacoub Magdi
Published: June 2023

Introduction:
Cardiac fibroblasts (CFs) have a crucial role in ECM remodeling as well as influencing contractility through crosstalk with the cardiomyocytes. There is accumulating evidence that the phenotype of CFs is disease specific. We here investigate the transcriptome signature of CFs in HCM patients and their functional significance.
Methods:
Primary CFs were isolated from the myectomy specimens of 12 clinically phenotyped HCM patients and 3 controls. RNA library was prepared from the cell isolates, and whole transcriptome sequencing was performed. Differential expression analysis was carried out using the Tuxedo pipeline. Pathway, Gene Ontology (GO) enrichment, and gene network analyses were performed using Ingenuity Pathways Analysis (IPA) and Gprofiler, respectively. Expression of candidate genes was validated using real time PCR, ICC, immunohistochemistry, cytokines profiling and western blotting.

Results:
Whole transcriptome analysis identified 292 significant differentially expressed genes (DEGs) (pvalue <0.05 threshold) in HCM fibroblasts compared to controls. The DEGs identified with the highest significance were associated with the “Cardiovascular System development and Function” network (1.55e-27 <pvalue< 3.10e-08). The most significant GO terms identified were associated with ECM remodeling, collagen binding, signal receptor binding, circulatory system development and biological adhesion and other relevant processes. The DEGs encompassed gene families such as collagens (
COL7A1, COL17A1, COL21A1, COL15A1 and COL5A3
), proteases (
MMP9, MMP12, ABI13BP
and
ADAM19
), fibulins (FBLN1 and FBLN5), inflammatory and signaling cytokines (
IL6, CCL2, CCL4, CCL11, IGF2, CSF1, FGF16
and
FGF2
), integrins and signaling receptors (
ITGA4, ITGA7, NRP2, SULF2, ADORA2B, CXCR4, FOLR2, PLXNA4
and
TREM2
) and kinases (
DDR1, EFNB2, RGCC, MAPK11, CDKN2B, PTK7, MARCKSL1, ROCK2, MET, TYROBP
and
KSR1
). Assessment of candidate genes was further performed by studying their expression patterns in patients’ samples (CFs extracts and tissue sections).
Conclusion:
Transcriptome signature of CFs derived from HCM identifies new candidate genes and pathways for ECM remodeling, collagen binding and pro-inflammatory signaling.
Abstract 14982: Use of Electronic Health Records to Develop an Actionable Taxonomy of Patients With Persistent Hypertension
Authors: Lu Yuan , Hu Cindy , Khidir Hazar , Caraballo Cesar , Mahajan Shiwani , Spatz Erica S , Curry Leslie , Krumholz Harlan M
Published: June 2023

Introduction:
Digital transformation of medical data present opportunities for novel approaches to manage patients with persistent hypertension (HTN).

Methods:
This qualitative study was a thematic analysis of clinician notes in the electronic health records of patients in the Yale New Haven Health System. Eligible patients were 18 to 85 years and had blood pressure >=160/100 mmHg at 5 or more consecutive outpatient visits between 1/1/2013 and 12/31/2018. 4,828 patients met criteria. We used conventional qualitative content analysis to develop a pragmatic framework of themes that distinguishes patients with persistent hypertension by their contributing factors. A random sample of 116 records were reviewed and analyzed when no new concepts emerge from analyses of subsequent data.

Results:
Of 116 patients, mean age was 64.5 (SD, 13.2) years; 55 % were female; 66 %, 21%, and 9% were White, Black, and Hispanic. The three themes emerged: (1) non-response to treatment, where patients were highly medically complex and biological resistance or secondary causes of HTN were significant components of their persistent HTN; (2) non-intensification of treatment, where issues such as provider specialty purview, competing medical priorities, patient preference, and concerns of white coat HTN contributed to treatment plans not being adjusted; (3) non-implementation of treatment plan, where varied concerns including a disconnect in patient education, difficulty obtaining medications, psychosocial barriers, or medication in tolerance caused appropriately escalated treatment plans to not be enacted.

Conclusions:
Our thematic analysis of patients’ medical records provides insights into actionable factors contributing to persistent HTN. These findings lay a foundation for designing digital tools for health systems to rapidly identify people with persistent HTN and connect them with targeted interventions at scale.
Abstract 14995: Outcomes of Transcatheter Aortic Valve Replacements in Patients With Left Ventricular Assist Device
Authors: Bandyopadhyay Dhrubajyoti , Malik Aaqib H , Goel Akshay , Gupta Rahul , Shah Ravi , Hajra Adrija , AHMAD HASAN
Published: June 2023

Background:
The development or progression of aortic insufficiency (AI) to moderate to severe in patients with left ventricular assist devices (LVADs) for end stage heart failure has been increasingly recognized and occurs in 30-40% of patients with continuous flow LVADs. This can lead to reduced efficiency of the LVAD and is associated with increased rates of hospitalizations and mortality. Up to 30% of LVAD patients with moderate to severe AI require surgical valve closure or replacement, which is high risk. More recently, case reports demonstrated transcatheter aortic valve replacement (TAVR) is feasible in LVAD patients with symptomatic AI, but there is a lack of large-scale study.

Methods:
National Readmission Databases (NRD) from 2015 to 2019 were used to identify hospitalizations with International Classification of Diseases-9th Revision and International Classification of Diseases-10th Revision procedural codes for TAVR in patients with and without LVAD. The outcomes of interest were mortality and 30-day readmission rate.

Results:
We identified a total of 245,176 TAVR hospitalizations. Among them, 146 (0.001%) had LVAD. LVAD patients undergoing TAVR were significantly younger (mean age 67.5 years vs. 79.6 years; P: <0.001) and had more comorbidities such as arrhythmias, peripheral vascular disease, chronic kidney disease, and anemia. On univariate analysis, LVAD patients demonstrated higher mortality (OR 4.88; 95% CI 2.17 - 11.02; P: <0.001), however, multivariate analysis showed this trend to be insignificant (OR 1.91; 95% CI 0.74-4.96; P= 0.184). Overall, patients with LVAD undergoing TAVR did have an increased length of stay and higher cost of hospitalization (P<0.001). We have witnessed the increasing trend of TAVR use in LVAD patients in the last five years (P: 0.009). After the propensity match, the 30-day readmission rate was not statistically significant (26.5 vs. 25%, P: 0.84).

Conclusion:
In our analysis, the mortality and 30-day readmission of LVAD patients undergoing TAVR were not significantly higher compared to non-LVAD patients. However, this finding may be limited due to the relatively small number of patients. Overall, this study indicates that TAVR may be considered in the appropriately selected LVAD patients.
Abstract 15005: Tlr4/py14-Caveolin-1-Mediated Endothelial C-iap2 Expression During Schistosomiasis-Associated Pulmonary Arterial Hypertension
Authors: Villarreal Elizabeth S , Erewele Ejehi , Castellon Maricela , Schwartz Andrew , Williams David L , Morrell Nicholas W , Bonini Marcelo G , Silva Claudia L , Lutz Sarah E. , Erzurum Serpil , Minshall Richard D , Oliveira Suellen D
Published: June 2023

Introduction:
During schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH), hyperproliferation of abnormal endothelial cells (ECs) contributes to development of severe vascular lesions within the lungs; a life-threatening phenomenon that remains with no target therapy.

Hypothesis:
Here, we found that antigenic molecules from the major etiological agent of Sch-PAH, i.e.,
S. mansoni
, amplify the secretion of the antiapoptotic protein c-IAP2 via TLR4-pY14Cav-1 signaling pathway, which we hypothesized to contribute to generation of an EC memory of survival and severity of PAH.

Methods/Results:
Cav-1 deficiency via shedding of extracellular vesicles (EVs) leads to survival of an apoptosis-resistant EC phenotype during idiopathic PAH. Similarly,
S. mansoni
egg antigens also reduced lung EC-Cav-1 expression, suggesting that Cav-1 also plays a role during pathogen-associated PAH. Cav-1 depletion via EVs precedes its phosphorylation at residue Tyr14 (pY14Cav-1), which in turn, contributes to EV loading. Among apoptotic regulators, IAPs have been found as a cargo of EVs in different conditions, including in TLR4-activated cells. Accordingly, our data indicates that
S. mansoni
egg antigen p40 also activated TLR4/NFkB-mediated signaling, inducing c-IAP2 expression and a time-dependent phosphorylation of Cav-1 in human lung microvascular EC (HMVEC-L: 228.2 +/- 38.28% of control; p<0.05; n=4). Moreover, although Sm-p40 alone was unable to induce shedding of EVs, combination with NFkB-associated proinflammatory mediators (TNF-α, IL-6, and ATP), significantly increased EV shedding by HMVEC-L, suggesting that
S. mansoni
may epigenetically prime ECs, but co-factors are required to induce EV shedding. Finally, Sch-PAH model using EC-

Cav1
-/-

mice (

End-scl.Cre
ERT2
;Rosa
mt/mg
;Cav1
fl/fl

) revealed that Cav-1 absence led to accumulation of eggs within the lungs and loss of eGFP+ cells, indicating that EC-Cav-1 phosphorylation may be required to development of Sch-PAH.

Conclusions:
Our data suggest that
S. mansoni
-induced pY14Cav-1 is associated to expression of the anti-apoptotic c-IAP2 protein, which may be critical for prolonged survival of a pathogenic EC phenotype during the development of Sch-PAH.
Abstract 15008: Hydrogel-Mediated Sustained Intra-Pericardial Delivery of Endothelial Colony-Forming Cells-Derived Extracellular Vesicles Promote Cardiac Repair Post-Myocardial Infarction
Authors: Gomes Karina P , Ross Maia , Jadli Anshul S , DiMarzo Nadia , Belke Darrell D , Fedak Paul W , Patel Vaibhav B
Published: June 2023

Introduction:
Myocardial infarction (MI) is a leading cause of death worldwide. Although available treatments improve prognosis post-MI, they do not remediate cardiomyocyte death and loss of cardiac vasculature, resulting in chronic maladaptive remodeling and subsequently, heart failure. Extracellular vesicles (EVs) derived from endothelial colony-forming cells (ECFCs) show therapeutic potential, facilitating adaptive cardiac remodeling post-MI. However, ECFCs function is compromised in patients with type-2 diabetes, a common risk factor for MI, limiting the applicability of autologous cell-based therapies. Therapeutic administration is a further challenge, as current strategies present difficulties regarding invasiveness, retention, and efficacy.

Hypothesis:
We hypothesized that the minimally invasive intra-pericardial (IP) injection of ECFCs-EVs within a hydrogel would improve cardiac retention and promote sustained therapeutic release, facilitating cardiac repair in a murine model of MI. We anticipated that this repair would be greater with the use of EVs derived from wildtype mice than from diabetic mice.

Methods:
The impact of wildtype and diabetic ECFCs-EVs was evaluated on both in vitro EVs retention and angiogenesis. In a murine model of MI, the left anterior descending coronary artery was ligated while the pericardium was preserved. We evaluated whether IP injection is an effective and safe method of delivering hydrogels containing ECFCs-EVs, in addition to its long-term effects on cardiac morphology and function.

Results:
Our findings indicate that hydrogel use facilitates sustained EVs release. Besides that, the administration of ECFCs-EVs increased coronary endothelial cell proliferation, migration, and vascularization in vitro, and reduced maladaptive cardiac remodeling, improving cardiac contractility and function in vivo. These effects appear to be more pronounced with the administration of wildtype ECFCs-EVs.

Conclusions:
Collectively, our results underscore the therapeutic promise of ECFCs-EVs to improve cardiac repair after MI.
Abstract 15019: Safe Implantation of Remote Pulmonary Artery Pressure Monitoring System (CARDIOMEMS) in a Pregnant Patient With Severe Heart Failure
Authors: Ahmad Javaria , Awwab Hajra , Thibodeaux Brittin , Faucheaux Lillian , Cooper Danielle , Barrilleaux Perry , Lewis Davis , Dominic Paari
Published: June 2023

Introduction:
Heart failure (HF) in pregnancy is associated with high maternal and neonatal mortality. Remote pulmonary artery pressure (PAP)-guided management of HF has been shown to reduce hospitalizations and mortality in HF patients. However, PAP monitoring systems (CardioMEMS) have not been implanted during pregnancy. We describe the first case of safe implantation of CarioMEMS in a pregnant patient with HF.

Case report:
A 38-year-old female with past medical history of non-ischemic cardiomyopathy with an ejection fraction of 15%, left ventricular thrombus, pulmonary hypertension, and atrial fibrillation was found to be 14 weeks pregnant by the obstetrician, and her HF medications were appropriately discontinued. The patient was continued on metoprolol, amlodipine, and enoxaparin and was advised to terminate the pregnancy due to high risk of maternal mortality, however, she decided against it. An interdisciplinary team of obstetricians and cardiologists managed the patient during her pregnancy. As the pregnancy progressed, the patient had multiple hospitalizations due to decompensated HF. To optimize her hemodynamic status and guide diuretic therapy, a decision to implant CardioMEMS was made after a risk-benefit discussion, at 23 weeks of gestation. A long wire and sheath were used from a femoral venous access to limit fluoroscopy. A right heart catheterization was performed, and cardiac filling pressures and output were measured. Minimal contrast (7.5 ml of iodixanol) was used to perform selective pulmonary artery angiography and the sensor was implanted according to manufacturer recommendations. Total fluoroscopic exposure during the procedure was 11.2 minutes (183 Gy-cm2). Patient’s diuresis and afterload reduction was adjusted based on PAP.

Conclusion:
Remote PAP monitoring system can be safely implanted in pregnant patients using limited contrast and fluoroscopic exposure to proactively manage heart failure.
Abstract 15020: Activation of Mitochondrial Bk
Ca
Channels Improves Hemodynamics and Normalizes Phosphoproteomic Changes in Pigs Following Cardioplegic Arrest and Cardiopulmonary Bypass
Authors: Ma Wenzhuo , Sodha Neel , Kolodziejczak Martin , Zhang Zhiqi , Huck Scarlett , Aboulgheit Ahmed , Muller Clarissa , sellke frank , Feng Jun , Terentyev Dmitry , Clements Richard T
Published: June 2023

Introduction:
BKCa channels are large conductance Ca++-activated K+ channels, which reside in the inner mitochondrial membrane in cardiomyocytes. We have demonstrated that the BKCa channel activator rottlerin (a.k.a mallotoxin) is cardioprotective during cardioplegic arrest in isolated rodent hearts and in vitro models. Here we used a clinically relevant in vivo swine model of cardioplegic arrest and cardiopulmonary bypass (CP/CPB) with and without rottlerin supplemented CP solution. Mitochondrial signaling alterations were identified by TMT-MS analysis of phosphorylation enriched mitochondrial protein fractions.

Methods:
Yorkshire swine (50 Kg) of both sexes were subjected to hypothermic CP/CPB (1hour) followed by 1 hour reperfusion. Groups included sham (n = 5), CP/CPB alone (n = 8) and CP/CPB with rottlerin supplemented cardioplegia (1uM) (CP/CPB+R) (n = 7). Mitochondria-enriched fractions were isolated from the left ventricular free wall and subjected to Tandem Mass Tag (TMT) labeling coupled mass spectrometry analysis.

Results:
CP/CPB pigs had reduced myocardial function indicative of myocardial stunning as shown by decreased LVDevP, and ±dP/dt vs sham (P<.05). BKCa activation significantly restored left ventricular function compared to CP/CPB alone (LVDevP: 74.0 ± 2.8
vs
. 52.5±5.0 mmHg, P < .01, +dP/dt: 1482±116
vs
. 923±126 mmHg/s, P < .01, and - dP/dt: 1120±116
vs
. 629±82 mmHg/s, P < .01). TMT-MS analysis identified 3363 proteins. 410 unique as well as numerous novel phosphorylation sites were significantly regulated in CP/CPB vs sham. Rottlerin treatment generally normalized phosphorylation changes with 175 and 63 different vs CP/CPB and sham, respectively. Enrichment analysis demonstrated significant changes in pathways associated with adrenergic and PKA signaling, calcium handling, mitochondrial dynamics, cristae organization, and oxidative phosphorylation.

Conclusions:
BKCa-activator supplemented cardioplegia significantly improves myocardial functional recovery following CP/CPB in a clinically relevant large animal model. Furthermore, mitochondrial BKCa-channel activation during cardioplegic arrest normalizes numerous signaling alterations associated with myocardial stunning and cardiac surgery.
Abstract 15023: Minimum Electrode Spatial Resolution for Arrhythmia Rotor Detection and Localization
Authors: Gandara Maria Ines , Aras Kedar K , Efimov Igor
Published: June 2023

Introduction:
Efficacy of electrotherapy or ablation therapy for treatment of arrhythmias is dependent on accurate detection of arrhythmia focal or reentrant drivers. However, success rates have been inconsistent, with frequent arrhythmia recurrence. A likely reason is the limited current spatial resolution of mapping devices, which averages 4 mm. The goal of this study was to determine the minimum spatial resolution necessary to identify and localize arrhythmia reentrant drivers (rotors).

Methods:
We conducted dual-sided (epicardial and endocardial) optical mapping studies in 12 donor human right ventricular wedge preparations subjected to arrhythmia induction protocol (S1S1 restitution and/or 50Hz burst pacing). The resulting arrhythmia data (0.7mm spatial resolution) was down sampled to different spatial resolutions (1.4-7mm) and up sampled back to full resolution. Rotors were tracked for each sub-resolution and compared to the rotors in the original data. Further comparisons were made according to arrhythmia type, sex, anatomical region, and mapped surface.

Results:
Rotor detection accuracy for currently used mapping devices was found to be 57±4%. Localization accuracy was 61±7%. For the current average spatial resolution, clinical rotor detection and localization accuracies can be expected to fall within a confidence interval of 47-67% and 46-75%, respectively. For the spatial resolutions tested, detection accuracy was above 80% only for a resolution of 1.4 mm, while localization accuracy reached that value at 2.1 mm. Moreover, the arrhythmia type affected detection and localization accuracies, which decreased consistently with loss of spatial resolution for unstable arrhythmias and had steadier values for stable arrhythmias. When comparing mapped surfaces, rotor incidence was higher in the endocardium, likely due to the presence of adipose tissue on the epicardial surface. Differences in sex and anatomical region had no statistically significant impact.

Conclusions:
The spatial resolution of current devices is insufficient to map rotors accurately, especially for unstable arrhythmias. For both detection and localization accuracies to be above 80%, a resolution of at least 1.4 mm is required.
Abstract 15033: Chronic Thromboembolic Pulmonary Hypertension Patients Have Reduced Bi-Ventricular Myocardial Perfusion Reserve, Which Improves Following Pulmonary Thromboendarterectomy
Authors: Fan Lexiaozi , Lee Daniel C , Benefield Brandon C , Malaisrie S. Christopher , Cuttica Michael , Hsu Li-Yueh , Allen Bradley D , Schimmel Daniel R , Avery Ryan , Freed Benjamin , Kim Daniel
Published: June 2023

Introduction:
This study seeks to determine whether bi-ventricular myocardial perfusion reserve (MPR) is reduced in patients with chronic thromboembolic pulmonary hypertension (CTEPH) compared to a control group using quantitative myocardial perfusion MRI.

Methods:
We prospectively enrolled 4 CTEPH patients (55±14 years, 4 males) and performed stress-rest (10 min apart) protocol using our 5-fold accelerated radial perfusion sequence. In one patient, we repeated stress-rest perfusion acquisition following pulmonary thromboendarterectomy (PTE). As a control group, we retrospectively identified 8 subjects (49±12 years, 5 males) with no evidence of vascular late gadolinium enhancement or perfusion defects who underwent a similar stress-rest protocol. The pixel-wise stress-rest myocardial blood flow (MBF) maps and MPR were quantified for both the left ventricular (LV) and right ventricular (RV) free walls. Two sample t-test was used to compare between the CTEPH and control groups.

Results:
Figure 1a shows representative stress and rest MBF maps and the corresponding MPR values comparing a CTEPH patient and a control subject. Summarizing the results of all patients (Figure 1b), compared to the control group, the CTEPH group had significantly (p < 0.05) lower stress LV MBF (1.56 ± 0.34 vs. 2.66 ± 0.50 ml/g/min), RV MBF (1.48 ± 0.19 vs. 2.56 ± 0.53 ml/g/min), LV MPR (1.65 ± 0.43 vs. 2.32 ± 0.50), and RV MPR (1.59±0.46 vs. 2.50 ± 0.53), but non-significant difference (p > 0.05) in resting LV MBF (0.96 ± 0.12 vs. 1.21 ± 0.43 ml/g/min) and RV MBF (0.96 ± 0.14 vs. 1.07 ± 0.36 ml/g/min). In one patient, PTE improved RV MPR from 1.43 to 2.49 as well as LV MPR from 1.24 to 2.36.

Conclusions:
This study suggests that both RV and LV MPR are reduced in CTEPH patients compared with controls and that PTE may improve RV as well as LV MPR in CTEPH patients. Future studies include additional enrollment of CTEPH patients, determining the diagnostic and prognostic role of RV and LV MPR in the context of PTE.
Abstract 15038: Collateral Flow From the Right Coronary Artery Alone is Not Sufficient for Adult Alcapa: Clinical Case Report
Authors: CongYong Liu , zeng kuan , Yu Taihui , Zhang Lu , Li Jianfen , Jiang Huiqi , Gao Minnan , Li Jingwen , Wang Jingfeng , Yang Yanqi
Published: June 2023

Introduction:
Myocardial ischemia in adult ALCAPA (Anomalous left coronary artery from the pulmonary artery) may lead to sudden death as the first clinical presentation. Cardiac blood supply from the right coronary artery alone is not sufficient for an adult ALCAPA. The aim of the present study was to describe a clinical case of severe myocardial ischemia in an adult female with ALCAPA supplied by the right coronary artery alone.

Patient and Clinical data:
45-year-old female patient admitted to our hospital due to recurrent palpitation with tachypnoea after physical exertion for 2 years. Resting ECG on admission with ST-T changes and frequent premature ventricular contractions (PVC) indicated significant myocardial ischemia. Transthoracic echocardiography (TTE) showed dilated left ventricle (LVDd 64mm) with regional systolic dysfunction anterolateral and posterolateral with EF of 44% and dilated right coronary artery. An ALCAPA was observed with dilated caliber of 9 mm at ostium (Panel A) which was confirmed by computed tomographic angiography of the coronary artery and coronary angiography. Well-developed collateral vessels between peripheral right posterior descending (RPD) and distal left anterior descending (LAD) were demonstrated (Panel F). No collateral vessel was found between bronchial artery and ALCAPA. The bronchial arteries were visualized in normal size. The left coronary ostium was not found in the aortic root at aortography. The patient underwent anatomical reconstruction of left main coronary artery by using autologous pulmonary flap and recovered well postoperatively.

Results:
Postoperative ECG showed that the preoperative ST-T changes and PVC disappeared completely. Cardiac magnetic resonance imaging and TTE one month and 6 months postoperatively demonstrated continuously improved LV systolic function and myocardial perfusion posterolaterally and anterolaterally.

Conclusion:
Collateral flow from the right coronary artery alone is not sufficient for adult ALCAPA and completely surgical correction is necessary.
Abstract 15068: Regional Variation in Atrial Fibrillation Ablation Care for Medicare Beneficiaries Across the United States
Authors: Hanna Jonathan , Freeman James V , Hummel James , Curtis Jeptha P , Lin Zhenqiu , Akar Joseph , Khera Rohan
Published: June 2023

Background:
Despite recognition of the role of early ablation for favorable long-term outcomes in atrial fibrillation (AF), access to these services requires substantial resources and expertise. We investigated county-level variation in the availability of AF ablation care for the Medicare population.

Methods:
In Medicare physician claims from 2019 linked to AHRQ county characteristics, we evaluated the volume of AF ablation per 100,000 population over the age of 65 years across US counties. We examined county characteristics associated with local access to ablation care, evaluating county-level differences in population composition, cardiovascular risk factor burden, and access to primary care (number per 100,000 population).

Results:
A total of 64,055 beneficiaries received AF ablation care from 1,501 physicians across the US. Of 3,143 U.S. counties, 403 (12.8%) in 2019 had any ablation procedures. In counties with local ablation care, a median 182 beneficiaries per 100,000 persons ≥65 years of age underwent AF ablation, with a wide variation in volumes across counties - interquartile range 97 per 100,000 to 337 per 100,000 (
Figure).
Of the total estimated 49,238,690 persons ≥65 years of age across counties within the United States and District of Columbia, 18,639,381 (37.9%) resided in counties without AF ablation services in the same county. In adjusted analyses, counties without local AF ablation services did not differ in demographic characteristics or prevalence of cardiovascular risk factors but were characterized by lower access to primary care physicians and lower educational attainment among county residents (P<0.01 for both).

Conclusions:
Only 1 in 8 US counties has local AF ablation care, with over one-third of U.S. adults ≥65 years of age residing in counties without local services. Patient-centered care necessitates greater accessibility for many patients without proximity to AF ablation care, especially with expanding indications.
Abstract 15072: Targeted Atrial Inhibition of Parasympathetic Signaling With GiGo Inhibitory Peptides Attenuates Electrical Remodeling and Development of Persistent Atrial Fibrillation in a Canine Model
Authors: Pfenniger Anna , Yoo Shin , Johnson David , Zhang Wenwei , Panni Azaria , Burrell Amy , Mandava Suman , Rottmann Markus , Passman Rod S , Knight Bradley P , Arora Rishi
Published: June 2023

Background:
While vagal contribution to paroxysmal atrial fibrillation (AF) is well demonstrated, a role for parasympathetic signaling in persistent AF is less clear. We have shown marked atrial parasympathetic hyperinnervation in a canine rapid atrial pacing (RAP) model of AF. However, the role of these new nerves in AF development is unknown.

Hypothesis:
RAP-induced parasympathetic hyperinnervation contributes to the onset and maintenance of AF, and a gene therapy approach inhibiting muscarinic M2 signaling (Gα
i
and Gα
o
- GiGo) in the atria can prevent persistent AF.

Methods:
Plasmids expressing GiGo inhibitory peptides (GiGo_ct) were injected in the atria of 7 dogs followed by electroporation to facilitate gene delivery. RAP was performed for up to 12 weeks. At terminal EP study, residual AF was recorded in the posterior left atrium (PLA), left atrial free wall (LAFW) and left atrial appendage (LAA). Regional atrial ERP was measured.

Results:
Controls developed ≥30 minutes of AF after a median of 4 days, and persistent AF (≥8 hours) after a median of 14 days. GiGo_ct delayed onset of AF of ≥30 minutes, and attenuated development of persistent AF. ERP was markedly shortened in the PLA and LAA of controls, and this was attenuated by GiGo_ct (p<0.001). Residual AF was slower (lower dominant frequency; PLA 9.4±0.6Hz Vs 11.0±0.7Hz; LAFW 7.8±0.3Hz Vs 10.4±0.7Hz; LAA 8.9±0.6Hz Vs 9.9±0.5Hz p<0.01), less fractionated (longer fractionation interval; PLA 70.0.4±5.2ms Vs 68.1±5.2ms; LAFW 98.8±4.1ms Vs 70.9±3.1ms; LAA 88.9±7.8ms Vs 80.3±2.0ms p<0.01) and more organized (lower Shannon's entropy; p<0.05).

Conclusion:
Newly sprouted atrial parasympathetic nerves play a functional role in development of persistent AF. Gene-based, selective M2 signaling inhibition by GiGo_ct attenuates electrical remodeling and prevents initiation and maintenance AF. Future optimization of gene therapy targeting autonomic remodeling may lead to novel, mechanism-guided treatments for AF.