bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12575: Diagnoses Associated With Telemedicine Use in Cardiology Clinics During the COVID-19 Pandemic
Authors: Shan Rongzi , Chen Jenny Y , Cho David
Published: November 2023

Introduction:
The COVID-19 pandemic led to widespread adoption of telemedicine, which has persisted in healthcare delivery. We aimed to characterize telemedicine use in ambulatory cardiology clinics over 2 years following onset of the COVID-19 pandemic.

Question:
What diagnoses are associated with telemedicine use in cardiology appointments?

Methods:
In this retrospective cohort study, demographic and encounter data of all cardiology clinic and telemedicine visits in the University of California Los Angeles (UCLA) Health System from 3/16/2020 to 6/27/2022 were obtained. Encounters were included if they were conducted by physicians, complete with ICD-10 codes, and not missing demographic data. Mixed effects logistic regression was used to model the association of diagnosis class (based on ICD-10 codes) with whether encounter was scheduled as telemedicine, adjusting for age, sex, race, ethnicity, social vulnerability index, date, and zip code.

Results:
The analysis included 72,878 patients (49.8% women, age 61.5 ± 17.2 years, 57.2% white, 12.5% Hispanic, 82.6% with zip code in a UCLA Health service area) over 248,373 encounters. Each patient had a median of 2 encounters (range 1-82). Of all encounters, 27,894 (11.2%) were scheduled as telemedicine. Telemedicine was more likely used in management of chronic conditions, especially metabolic disorders (adjusted OR [aOR] 2.26, 95% CI 2.10-2.44) and cardiomyopathies (aOR 2.10, 95% CI 1.93-2.28), than for evaluation of undifferentiated signs/symptoms. Telemedicine was less likely used for general exam/screening (aOR 0.52, 95% CI 0.46-0.58) and heart transplant (aOR 0.51, 95% CI 0.50-0.64;
Table
).

Conclusion:
In this study, the most established use case for telemedicine in cardiology was care of chronic cardiac diagnoses among non-transplant patients. Ongoing maintenance of chronic cardiovascular conditions through telemedicine may be a sustainable healthcare delivery model post COVID-19 pandemic.
Abstract 12577: Sex Differences in Outcomes of Percutaneous Coronary Intervention for Stable Coronary Artery Disease in Patients With End Stage Kidney Disease
Authors: Mahdi Ahmad , Mehta Harsh , Chan Wan Chi , Vasudeva Rhythm , Vindhyal Mohinder Reddy , Trupp Caroline , Greene Amelia , Munshi Kartik , Tadros Peter , GUNASEKARAN PRASAD , Jiwani Sania , MUNGUTI CYRUS , Ramani Gokul , Hajj Georges , Wiley Mark , Hockstad Eric , gupta Kamal
Published: November 2023

Introduction:
End Stage Kidney Disease (ESKD) patients are at a higher risk of morbidity and mortality from cardiovascular diseases, particularly coronary artery disease (CAD). There is paucity of sex related differences in percutaneous coronary intervention (PCI) outcomes in this population.

Methods:
Patients ≥ 18 years with ESKD on dialysis for at least 3 months and who underwent PCI for stable CAD between years 2010 and 2018 were identified from the United States Renal Data System (USRDS) database. Appropriate ICD-9/10 codes were used to identify the relevant conditions and procedures. Statistical analyses were performed using the SAS 9.4 software.

Results:
A total 23,115 ESKD patients underwent PCI, of which 42.5% were women. While there was a declining trend of utilization of PCI (Men: 6.6 to 2.8; Women: 6.6 to 2.7 procedures per thousand ESRD patients; p<0.001), the in-hospital mortality (Men:1% to 3.2%, p<0.001; Women:0.7% to 2.8%, p<0.001), 30-day mortality (Men:3% to 6.8%, p<0.001; Women:3.5% to 5.2%, p<0.001) and 1-year mortality (Men: 25.6% to 32.7%, p<0.001; Women: 27.7% to 30.4%, p<0.001) as well as 30-day myocardial infarction (Men: 2.7% to 4%,p<0.001; Women:3.1% to 5.6%, p<0.001) increased in both sexes during the study period. After propensity matching, hospital length of stay (3 days vs 4 days, p<0.001), 30-day readmission (29.4% vs 33.1%, p<0.001) and 1-year incidence of stroke (2.3% vs 3.3%, p<0.001) were higher in women, while other outcomes were not significantly different between men and women.

Conclusions:
Despite the decreasing utilization of PCI for stable CAD in ESKD patients over the study period, worsening short- and long-term mortality was observed in both sexes. Women were more likely to have a longer hospital stay as well as readmission within 30 days post-procedure.
Abstract 12579: Intracoronary Thrombolysis, an Option in Coronary Arteries With Unique Characteristics: A Case Series Report
Authors: Orozco Martin Jose Ramon R , PONCE DE LEON ENRIQUE , Kuri Ayache Mauricio , Rodriguez Salinas Cesar Alejandro , Cesena Victor Javier , Garcia Corral Roberto , Mejia Fernando , Mendez Rodriguez Allan , Morales Escajeda Jesus ivan
Published: November 2023

Cases Description:
Case 1:
A 47-year-old male with inferior ST-segment Elevation Myocardial Infarction (STEMI). Percutaneous Coronary Intervention (PCI), showed an ectasic Right Coronary Artery (RCA) with an occlusive thrombus in mid-distal segment, TIMI 0. Thromboaspiration was not successful, proceeding to use intracoronary (IC) Alteplase 15mg. 72 hours later, PCI showed a RCA without stenosis, TIMI 2. Intravascular Ultrasound (IVUS) was used, showing no plaques or dissection. Discharged with Rivaroxaban 20mg QD and Acetilsalicylic acid (ASA) 100mg QD.

Case 2:
A 38-year-old male, with previous PCI and 1 stent in Anterior Descending Artery (ADA); arrives with STEMI. PCI showed a ADA non-occlusive intrastent thrombus, TIMI 2. IC Alteplase 15mg was used. After 72 hours, PCI identified the ADA with TIMI 3 flow. IVUS and Optical Coherence Tomography (OCT) showed a mild intrastent thrombus and proximal infraexpansion of previous stent. Proximal and medial segments were dilated, and 1 stent was placed distal. IVUS showed adequate expansion. Discharged with Apixaban 5mg BID and Clopidogrel 75mg QD.

Case 3:
A 64-year-old male, with inferior STEMI. PCI shows an ectasic ADA with a proximal and medial segment thrombus, TIMI 2. Tromboaspiration and posterior IC Alteplase 15mg were used, with TIMI 3 result. PCI 24 hours later, shows the ADA with TIMI 3 flow. IVUS identifies that no angioplasty was needed. Discharged with Ticagrelor 90mg BID and ASA QD.

Discussion:
IC thrombolysis is a useful method in primary PCI, where there is no favorable anatomy or massive IC thrombus. These cases show the utility of using IC imaging to evaluate the anatomy and thrombotic content of angiographic lesions. There is no consensus in the chronic anticoagulation/antithrombotic management after IC thrombolysis.
Abstract 12580: Impact of Zero Coronary Artery Calcium on Downstream Cardiac Testing
Authors: Lin Ethan Y , Alonzo Rea , Fang Jiming , Chu Anna , Elhadad Levi , Basque Shalane , Wijeysundera Harindra C , Hanneman Kate A , Nguyen Elsie T , Farkouh Michael E , Udell Jacob A , Roifman Idan
Published: November 2023

Introduction:
While coronary artery calcium scoring (CAC) has emerged as a useful tool for cardiovascular disease (CVD) risk prediction, its impact on downstream resource use remains unclear, especially in those with zero CAC. The purpose of this study was to determine the relationship between zero CAC and downstream use of cardiac procedures.

Methods:
Consecutive CAC scores from two academic hospitals in Toronto, Canada, from 2011 - 2019, were linked to population-based databases. Subjects with zero calcium without previous CVD were subsequently propensity score-matched with a non-CAC-tested control group for age, sex, CVD risk factors and comorbidities relevant to receipt of testing. Downstream cardiac testing, myocardial infarction (MI), stroke, and congestive heart failure (CHF) hospitalizations were compared between the two groups. Results were analyzed using descriptive statistics and Cox proportional hazards regression models.

Results:
4,884 patients (Mean 56.8y, SD 11.3) underwent CAC scoring, of whom 2,709 (55.5%) had zero CAC (Mean 52.9y, SD 10.6, 55.4% women). Compared to those not tested at 90 days, zero CAC subjects had similar graded exercise stress test (GXT) (72 tests vs 60, p = 0.29), stress echocardiography (40 vs 32, p = 0.34) and myocardial perfusion imaging (MPS) (26 vs 37, p = 0.15), but higher cardiac MRI (CMR) (48 vs 7, p < 0.001) use. At 3.4 years, GXT (HR 1.24, 95% CI 1.14 - 1.35), stress echocardiography (HR 1.80, 95% CI 1.59 - 2.05) and CMR (HR 3.40, 95% CI 2.55 - 4.53) use was higher in the zero CAC group, whereas MPS (HR 1.08, 95% CI 0.97 - 1.21) and catheterization (HR 1.14, 95% CI 0.91 - 1.44) were similar and PCI (HR 0.59, 95% CI 0.35 - 0.98) and CABG (HR 0.14, 95% CI 0.03 - 0.61) were lower. There was an approximately 5-fold lower rate of MI (HR 0.22, 95% CI 0.10 - 0.51) in the zero CAC group at 3.4 years and no difference in stroke (HR 0.98, 95% CI 0.46 - 2.05) or CHF hospitalizations (HR 1.15, 95% CI 0.53 - 2.48).

Conclusion:
Zero CAC was associated with higher use of some non-invasive cardiac testing, similar use of catheterization, and reduced PCI, CABG and AMI when compared to a propensity score-matched control group. The results support the utility of a zero CAC in limiting invasive procedures while maintaining an association with reduced cardiac events.
Abstract 12585: The Impact of Remote Patient Monitoring and Digital Therapeutics on Major Clinical Events and Costs in Heart Failure Patients: Early Experience in the Quebec Public Healthcare System
Authors: Marier Tetrault Emmanuel , Aver B Ribeiro Paula , El Haffaf Mouny , Bechard Stephanie , Brouillard Philippe , Bebawi Emmanuel , Yuan Shuaiqi , Hanh Vo Thi Xuan , Khazaka Michael , Nguyen John , Carrier Zoe , El Kamouni Karim , Pomey Marie-Pascale , Tournoux Francois
Published: November 2023

Introduction:
There is increasing use of digital health solutions in heart failure (HF), but few studies have demonstrated its impact on public healthcare systems in North America. The Continuum project developed a mobile app for remote patient monitoring (RPM) and a digital therapeutics (DTx) solution aimed at assisting clinicians in medication optimization and preventing hospitalizations among HF outpatients.

Research Question:
Are RPM and DTx cost-effective for care of outpatients with HF?

Methods:
A 3-month randomized controlled trial for HF outpatients at risk of hospitalisation evaluated the Continuum program versus standard of care alone. This 12-week program included: 1. A self-care app via smartphone or tablet where patients entered vital signs, weight, and HF symptoms; 2. Remote monitoring of these data by clinical nurses; 3. DTx automated medication suggestions sent to the treating medical team; and 4. HF educational modules for patients.

Results:
A total of 171 patients were included. Preliminary results are available for the first 63 patients that completed the study, 32 intervention (INT) and 31 control (CTRL). Patients were similar in age (70±12 vs 69±13y), NYHA class (II 81 vs 87%), patients with ejection fraction <40% (56 vs 48%) and comorbidities such as diabetes (38 vs 45%; INT vs CTRL). The number of emergency room (ER) visits and/or hospitalisations (all cause) per patient was 0.19±0.47 for the INT group and 0.55±0.89 for the CTRL one (P=0.05). Survival analysis (Figure) showed a trend in favor of the INT group (95 days (CI95% 87-104) vs 78 days (CI95% 68-89); P=0.08). The total cost of healthcare consumption (hospitalizations + ER visits) in the INT group was 134,088 Canadian dollars vs 174,924 in the CTRL group (+30%).

Conclusions:
Our preliminary results show potential benefits of a mobile app incorporating self-care, remote monitoring, and digital therapeutics in preventing major events in HF outpatients at a reduced cost for the healthcare system.
Abstract 12588: A Hyperactive Heart: A Case of Adderall-Induced Cardiomyopathy
Authors: Rose Christian J , Klein Max W , Hama Amin Ali
Published: November 2023

Introduction:
Stimulants are commonly used in the treatment of attention deficit hyperactivity disorder (ADHD). Cardiomyopathy is a rare but serious potential side effect of long-term stimulant use, even when done so for therapeutic purposes.

Case:
We present a 56-year-old female with ADHD and long-term high dose Adderall use who presented for progressively worsening dyspnea over the course of 1 year. Labs were notable for peak hs-troponin 246ng/L and pro-BNP 6598pg/mL. On admission, echocardiogram was notable for reduced left ventricular (LV) ejection fraction (EF) of 20-25% with normal LV wall thickness and mild-moderate valvular disease. ECG showed sinus rhythm 97 bpm, bi-atrial enlargement, normal voltage and no evidence of conduction delay. A left heart catheterization demonstrated no evidence of coronary artery disease. Cardiac MRI at 1.5T was notable for LVEF 18%, severe LV dilation (EDV 189mL/m2), severe right ventricular (RV) dilation (EDV 131mL/m2) with RVEF 26%, native T1 1099 msec, ECV 41%, normal T2*, and a very thin circumferential subendocardial late gadolinium enhancement involving the apical and mid segments (6% of LV mass). TSH, Vitamin B1, and selenium levels were normal, and there was no evidence of tachyarrhythmia throughout her admission. She denied significant alcohol use, illicit substance use, or family history of cardiomyopathy. The absence of paraprotein gap and other stigmata lowered suspicion for amyloidosis. Due to the results of her workup, her Adderall was discontinued as this was thought to be the likely cause of her newly discovered cardiomyopathy. She was discharged home on GDMT with close follow up with advanced heart failure.

Discussion:
The association between long-term stimulant use and cardiomyopathy is known, but not well described. Common cardiac effects of stimulants include tachycardia, hypertension and increased risk of arrhythmias, all of which are associated with increased workload on the heart and therefore contribute to the development of cardiomyopathy. Although generally rare, long-term use of prescription stimulant medications can contribute to the development of cardiomyopathy and should therefore be used sparingly and for the shortest period possible when necessary for the treatment of ADHD.
Abstract 13834: Prognosis of Patients With Atrial Fibrillation and Weight Loss: The Fushimi AF Registry
Authors: Iguchi Moritake , Hamatani Yasuhiro , Masunaga Nobutoyo , Ishii Mitsuru , Ide Yuya , Fujino Akiko , Yoshizawa Takashi , DOI KOSUKE , Ikeda Syuhei , Ishigami Kenjiro , Esato Masahiro , Wada Hiromichi , Hasegawa Koji , Ogawa Hisashi , Abe Mitsuru , Akao Masaharu
Published: November 2023

Background:
Atrial fibrillation (AF) is a common cardiac arrythmia in the elderly, in whom frailty is often a clinical issue. Weight loss is one of the key factors of frailty, and we previously reported that low body wight (≤50 kg) was associated with higher mortality and morbidity in patients with AF. However, the association of weight loss with prognosis of AF patients is unclear.

Methods:
The Fushimi AF registry is a community based prospective survey of AF patients in Japan. We collected data on body weight annually, and changes in body weight were obtained in 2,922 patients (mean age, 73 years; female 39.3%; mean body weight 59.8 kg). We defined weight loss as decrease in body weight
≥
4.5 kg or 5% in the past year based on the frailty-defining criteria in the Cardiovascular Health Study.

Results:
During the follow-up, 1319 patients had weight loss (7.9% per person-year). Patients with weight loss were older, and had more hypertension, diabetes, coronary artery disease, chronic kidney disease, and heart failure at baseline than those without. Prevalence of prior stroke/systemic embolisms (SE) and major bleeding were similar between patients with and without weight loss. In the logistic regression analysis, hypertension, diabetes, chronic kidney disease, and heart failure were positively associated with development of weight loss, and incidence of stroke/SE was inversely associated with weight loss. Landmark analysis after the onset of weight loss revealed that patients with weight loss showed significantly higher incidence of all-cause death and cardiac death. Incidence of heart failure hospitalization, stroke/SE, and major bleeding were comparable between patients with and without weight loss. After adjustment for clinical confounders, weight loss was significantly associated with the incidence of all-cause death (hazard ratio, 1.79; 95% confidence interval, 1.54-2.09) and cardiac death (hazard ratio, 1.67; 95% confidence interval, 1.15-2.43). Subgroup analyses revealed that weight loss was also significantly associated with higher all-cause and cardiac mortality regardless of age, sex, and body weight at baseline.

Conclusion:
In AF patients, weight loss was significantly associated with higher all-cause and cardiac mortality.
Abstract 13838: Hemostatic Disorder During Left Ventricular Assist Device Implantation in Swine
Authors: Reuter Johanna , Meissner Florian , Buechsel Martin , Straky Hendrik , Costa Galbas Michelle , Czerny Martin , Bothe Wolfgang
Published: November 2023

Introduction:
Implantation of left ventricular assist devices (LVAD) conventionally requires the use of cardiopulmonary bypass (CPB). Among others, mechanical circulatory support devices favor intraoperative hemostatic disorder.

Hypothesis:
Despite the high risk of severe bleeding and thromboembolic complications, little is known about the intraoperative extent of hemostatic disorder during LVAD implantation.This study aimed to determine the extent of hemostatic disorder during LVAD implantation in a porcine model under CPB and LVAD support, separately.

Methods:
We performed LVAD implantation in 10 female German Landrace pigs (body weight 104 ± 13 kg). Blood samples were collected three times: at (1) Baseline, (2) after CPB and (3) after LVAD. For CPB, cannulation of the left jugular vein and right femoral artery was performed. After sternotomy and pericardiotomy, apical coring was performed under CPB. A continuous-flow LVAD with transventricular outflow graft was implanted. For CPB and LVAD, a flow rate of 3-7 L/min and a rotational speed of 4000 to 7200 rpm were aimed, respectively. Hemostatic laboratory markers from all times were compared by Wilcoxon signed rank test.

Results:
Compared to Baseline, CPB led to a significant decrease of fibrinogen and antithrombin as well as an increase of von Willebrand factor (vWF) ratio and D dimer (DD). Compared to after CPB, there was a continued decrease of antithrombin and an increase of DD, as well as a significant increase of vWF and vWF activity under LVAD support.

Conclusion:
Among others, CPB and LVAD separately contribute to hemostatic disorder during LVAD implantation. Human laboratory markers allowed early detection of intraoperative hemostatic changes in pigs. Further studies are needed to investigate whether off-pump LVAD implantation reduces perioperative hemostatic disorder.
Abstract 13842: A Macromolecule-Linked Prodrug of Rapamycin Shows Potent Growth Inhibitory Effects Against Activated Fibroblasts Mimicking Fibroproliferative Transformation in Pulmonary Hypertension
Authors: Alferiev Ivan S , Bratinov George , Frank David B , Fishbein Ilia , Chorny Michael
Published: November 2023

Introduction:
Pulmonary hypertension (PH) is a life-threatening disease characterized by a progressive loss of vascular cell homeostasis with an irreversible shift toward the activated proliferative phenotype. New drug delivery approaches with improved efficacy are urgently needed for better clinical management of the disease. The present studies evaluated a novel prodrug-based strategy designed to durably suppress PH through enhanced delivery of rapamycin. We hypothesized that a long-circulating rapamycin prodrug constructed with a bioeliminable polyethylene glycol (PEG) scaffold would show efficacy as a new anti-PH drug candidate in cell culture and animal model studies.

Methods:
A new carrier-linked prodrug was synthesized by reversibly attaching rapamycin to 4-arm PEG (PEG-[RAPA]
4
, Mn = 40 kDa). Cell growth inhibitory effects of the construct were studied
in vitro
with proliferative fetal lung fibroblasts (HEL299) and transformed fibroblast-type cells (SK-LMS1), and
in vivo
using SK-LMS1 xenografts established in athymic nude mice. The results were analyzed by comparing the growth curve slopes (one-way ANOVA with the Tukey post hoc test).

Results:
Rapamycin (1-5 μM) potently inhibited proliferation of both fetal and transformed fibroblasts (75-95% inhibition 7 days post-treatment) in PDGF-BB-stimulated growth conditions (40 ng/ml, 2% FBS). Serum-stimulated (10% FBS) growth of both cell lines was also suppressed with remarkable potency at all tested concentrations (≥50% and ≥65% inhibition for HEL299 and SK-LMS1, respectively). In animal model studies, PEG-[RAPA]
4
given 2х/week strongly mitigated disease progression throughout the 4-week treatment period, whereas all animals in ‘no treatment’ and ‘blank PEG’ control groups were eliminated after reaching the end point. Statistical analysis confirmed markedly delayed growth of SK-LMS1 xenografts in the prodrug group (p = 0.032).

Conclusions:
Polymeric carrier-linked prodrug delivery of rapamycin effectively inhibits growth of activated fibroblasts
in vitro
and in a preclinical model recapitulating the altered vascular cell phenotype and proliferative character of the human disease. PEG-[RAPA]
4
is a promising candidate for further evaluation as a potential therapy for PH.
Abstract 13851: CAR-T Cells: A Potential Novel Strategy for Mitigating Fibrosis in Duchenne Muscular Dystrophy
Authors: Marigny Celine , Revet Gaelle , Berger Anne , Boulch Morgane , Mougenot Nathalie , Bois Axelle , Collombat Victor , Bousta Sabrina , Lemaitre Mégane , Bot Adrian , Lafuste Peggy , Hagege Albert , Aghajanian Haig , BOUSSO Philippe Bousso , Agbulut Onnik , Menasche Philippe
Published: November 2023

Introduction:
Chimeric Antigen T (CAR)-T cells have proven effective preclinically for mitigating cardiac fibrosis in hypertensive cardiomyopathy.

Hypothesis:
We assessed whether this approach could be applied to Duchenne Muscular Dystrophy (DMD) by targeting Fibroblast Activating Protein (FAP)-expressing activated fibroblasts in cardiac and skeletal muscle fibrosis.

Methods:
A protocol for the lymphodepletion conditioning of mice was developed to optimize the dosing of cyclophosphamide. Next, immune-magnetically selected T cells were retrovirally transduced to target FAP (FAP-CAR) and quality-controlled by co-culture killing assays using FAP-expressing HEK target cells. Finally, lymphodepleted D2.
mdx
mice were intravenously injected with 10
7
FAP-CAR T cells (n=9) or 10
7
GFP-T cells (n=9) or Bovine Serum Albumin (BSA, n=8). Cardiac and skeletal muscle end points were assessed 2 and 5 weeks after treatment.

Results:
In vitro
, the engineered CAR-T cells expressed activation markers (CD69, PD-1) and released large amounts of granzyme, perforin and interferon γ upon exposure to FAP-expressing target cells. One IP injection of cyclophosphamide (3mg) 4 days before treatment was safe and induced a lymphodepletion which enabled robust
in vivo
expansion of FAP-CAR T cell assessed by flow cytometry in lymphoid organs and blood: 10
5
, 2.10
6
and 10
7
detected CAR-T cells at day 3, 5 and 7 post-injections, respectively. This was paralleled by a more than a 2-fold decrease in endogenous FAP expression in skeletal muscles, as assessed by PCR at day 5 post-injections, and measurable FAP-CAR levels in the spleen compared with GFP-T cell controls.
In vivo
, FAP-CAR T cells significantly improved LV function with an EF change from baseline (Mean±SEM) of 33.1% ± 6.7% in FAP-CAR
vs.
3.7% ± 6.4% and -9.6% ± 7.9% in GFP-T and BSA (
p
<0.037 and
p
<0.005, respectively) at 2 weeks. The benefit was maintained at 5 weeks post-treatment. Several markers of fibrosis, particularly collagens 1 and 3, were also down-regulated in heart and muscles.

Conclusions:
FAP-CAR-T cells might represent a new therapeutic option for mitigating fibrosis in DMD, likely in conjunction with approaches aimed at addressing the root cause of the disease through a re-expression of a functional dystrophin.
Abstract 13857: Slit2/ROBO4 Ligand-Receptor Pair as Novel Biomarkers for Survival in Pulmonary Arterial Hypertension
Authors: Blatt Carly , Yang Jun , Barnes Allan , Griffiths Megan , Damico Rachel L , Simpson Catherine , Kolb Todd , Pauciulo Michael , Nichols Bill , Ivy Dunbar D , Austin Eric D , Hassoun Paul , Everett Allen D
Published: November 2023

Background:
Slit ligand guidance 2 (Slit2) is a ligand of the Roundabout guidance receptor (ROBO4), a transmembrane endothelial-specific receptor expressed in lung tissue. Pulmonary vascular remodeling contributes to PAH development and ROBO4 has been shown to play a role in inhibiting VEGF related angiogenesis. No studies have evaluated ROBO4 and Slit2 levels in PAH.

Research Question:
This study sought to assess if ROBO4 and/or Slit2 levels are detectable, altered in and associated with survival outcomes and hemodynamic measurements in patients with PAH.

Methods:
Serum ROBO4 levels were measured in 139 adults with PAH and 90 controls. Serum Slit2 levels were measured in 210 adults with PAH and 40 controls. Mann-Whitney U tests were used to compare biomarker levels in PAH and controls. Biomarker levels in the PAH cohort were compared to hemodynamic measurements and survival analyses were conducted for a composite outcome (death or transplant) using Cox proportional hazard models, and Kaplan Meier analysis with biomarkers dichotomized at the median.

Results:
ROBO4 and Slit2 levels were higher in PAH vs control patients (p=0.0005, p=0.002). In Kaplan-Meier analysis, ROBO4 and Slit2 levels above the median were associated with time to death or transplant (Logrank test p=0.016, p=0.03). ROBO4 and Slit2 levels were positively associated with death or transplant using Cox proportional regression, adjusted for age with a hazard ratio of 1.8 (95% CI 1.07-2.97, p=0.003) and 1.49 (95% CI 1.11-1.99, p=0.008), respectively. There were no statistically significant associations between ROBO4 and Slit2 levels and hemodynamic data such as mPAP, mRAP and PVR.

Conclusions:
This pilot data demonstrates that the angiogenic protein Slit2 and its receptor ROBO4 levels are both associated with survival outcomes in PAH. Future studies should evaluate in vitro studies to localize Slit2/ROBO4 in lung tissue using immunohistochemistry.
Abstract 13859: The Omics Signature of Human Pericardial Fluid Exosomes Reveals the Therapeutic Potential of APAF-1 Inhibition in Ischemic Heart Disease
Authors: Bellahcene Mohamed , Saif Jaimy , Sarkar Moumita , Anwar Maryam , Aday Sezin , Sedani Sunny , Guan Yingshu , Chamorro-Jorganes Aranzazu , Ruiz Polo de Lara Inigo , Heesom Kate , angelini gianni , Punjabi Prakash , Peer Dan , Emanueli Costanza
Published: November 2023

Background:
The human pericardial fluid (PF) contains heart-derived small extracellular vesicles (sEVs) able to induce vascular responses via microRNA (miR) transfer. People with diabetes (DM) are particularly at risk of severe ischemic heart disease (IHD) and might require personalized therapeutic treatment.

Hypothesis:
The PF-sEVs molecular profiling supports the identification of clinical-relevant therapeutic targets.

Aims:
1) To characterize PF-sEVs of IHD patients with/out type-2 DM (T2DM) in comparison to controls; 2) to validate the emerging therapeutic target candidates.

Methods:
PF samples (n=12/group) were collected during cardiac surgeries, namely CABG (for IHD with/out DM groups) and mitral valve repair (non-IHD, non-DM control group). sEVs were prepared (SEC), quality controlled (Nanosight and Exoview) and submitted to untargeted proteomics and microRNA array (Exiqon) or validation experiments. miRNA-target prediction methods and integration of proteomics and transcriptomics via networks identified differentially expressed pathogenic proteins and their putative endogenous miRNA regulators. The emerging dysregulated miRNA/protein axis was investigated
in vitro
and in mice with myocardial infarction (MI) and with/out diet-induced T2DM.

Results:
the PF-EVs of IHD patients with DM showed increased APAF-1 and reduced let-7b-5p, a miR which we have demonstrated to repress APAF-1 by direct 3’-UTR-binding. Exposure of endothelial cells (ECs) to DM and IHD-mimicking culture conditions increases APAF-1 level, triggering apoptosis and reducing angiogenesis. The phenotype of ECs kept under disease-mimicking conditions was rescued by APAF-1 silencing (siRNAs) and by supplementation with either healthy PF-EV or LNPs carrying let-7b-5p as sole miR cargo. The synthetic APAF-1 inhibitor ZYZ-488 improved post-MI cardiac function (Vevo3100 echocardiography), increased capillary density and reduced EC apoptosis in the peri-infarct area of diabetic and non-diabetic mice of both sexes.

Conclusions:
PF-EVs represent a novel and privileged source for the discovery of clinical-relevant therapeutic targets. APAF-1 inhibition holds value for post-ischemic cardiac protection and repair, including in diabetic people.
Abstract 13863: Computed Tomography Angiography Characteristics of Thin-Cap Fibroatheroma in Patients With Diabetes Mellitus
Authors: Suzuki Keishi , Kinoshita Daisuke , Niida Takayuki , Yuki Haruhito , Fujimoto Daichi , Dey Damini , Lee Hang , McNulty Iris , Takano Masamichi , Mizuno Kyoichi M , Ferencik Maros , Kakuta Tsunekazu , Jang Ik-kyung
Published: November 2023

Background:
It was recently reported that thin-cap fibroatheroma (TCFA) detected by optical coherence tomography (OCT) was an independent predictor of future cardiac events in patients with diabetes mellitus. However, OCT requires invasive procedure including intracoronary imaging. Computed tomography angiography (CTA) characteristics of TCFA have not been systematically studied.

Aims:
The aim of this study was to investigate CTA characteristics of TCFA in patients with diabetes mellitus.

Methods:
Patients with diabetes mellitus who underwent pre-intervention CTA and OCT were enrolled. Non-culprit lesions with a diameter stenosis of ≥30% on angiogram were assessed. Plaque volume and high-risk plaque (HRP) features were evaluated by CTA.

Results:
Among 132 plaques in 106 patients with diabetes mellitus, 31 plaques had TCFA. Fibrofatty and necrotic core (FF + NC) volume (-30 to 130 HU) was higher in TCFA than in non-TCFA (125.5 mm
3
vs. 59.4 mm
3
, p <0.001). The prevalence of positive remodeling (90.3% vs. 44.6%, p <0.001), low attenuation plaque (80.6% vs. 28.7%, p <0.001), and napkin-ring sign (77.4% vs. 11.9%, p <0.001) was significantly higher in TCFA than in non-TCFA. The difference in the prevalence of spotty calcification between TCFA and non-TCFA was not statistically significant (19.4% vs. 15.8%, p = 0.608). In multivariable logistic regression analysis, FF + NC volume ≥103.7 mm
3
(OR: 6.8; P <0.001) and HRP features ≥2 (OR: 11.7; P <0.001) were associated with TCFA. The addition of FF + NC volume ≥103.7 mm
3
to HRP features ≥2 significantly increased the area under the curve for detection of TCFA (AUC = 0.766 [95% CI; 0.673-0.859] vs AUC = 0.820 [95% CI; 0.736-0.904]; p = 0.012).

Conclusions:
FF + NC volume and HRP features on CTA were associated with OCT-detected TCFA. CTA may be helpful in identifying high-risk plaques in patients with diabetes mellitus.
Abstract 13872: CD70 Modulates Vascular Smooth Muscle Phenotype and Metabolism by Regulating Cellular Redox State
Authors: Pandey Arvind K , Waldeck-Weiermair Markus , Yadav Shambhu , Oldham William M , Michel Thomas , Loscalzo Joseph
Published: November 2023

Introduction:
The tumor necrosis factor superfamily (TNFSF) displays a wide array of vascular effects; however, the role of the TNFSF member CD70 is still being elucidated in the vasculature. We have recently described how CD70 modulates endothelial cell function and redox status by altering nitric oxide bioavailability and intracellular reactive oxygen species (ROS). However, the role of CD70 in vascular smooth muscle cells (VSMCs) is not known. We hypothesized that CD70 can alter VSMC phenotype and mitochondrial function through regulation of intracellular ROS.

Methods:
Human aortic VSMCs (AoVSMCs) were transfected with control or CD70-directed siRNA (n = 5-6). Cellular phenotype was assessed by scratch assay and collagen matrix gel contraction assay. Cell lysates were analyzed by Western blot and quantitative RT-PCR. Intracellular cytosolic hydrogen peroxide levels were measured using the fluorescent biosensor Hyper7 following stimulation by auranofin (50-70 cells per group averaged over 4 experiments). Metabolic profiling was performed with Seahorse assay, and mitochondrial membrane potential was assessed using TMRM dye (120 cells per group averaged over 3 experiments).

Results:
Following CD70 knockdown, AoVSMCs demonstrated augmented wound closure and decreased collagen matrix contraction. Expression of synthetic/proliferative markers, including vimentin, alpha-1 type I collagen, osteopontin, caldesmon-1, and c-Myc, was increased by up to 50%, and contractile markers including smoothelin, synemin, and synaptopodin-2 were decreased by up to 50%. Cytosolic hydrogen peroxide production was increased, with expression of NADPH oxidase (NOX) 4 and gp91phox (the catalytic subunit of NOX2) both increased by over 2-fold. CD70 knockdown led to a pronounced alteration in VSMC metabolic profile, with significantly decreased oxygen consumption rate (25%), extracellular acidification rate (45%), and maximal respiratory capacity (46%), as well as a decrease in mitochondrial membrane potential (37%).

Conclusions:
CD70 exerts a novel regulatory effect on VSMC phenotype; loss of CD70 promotes transition to a synthetic phenotype characterized by increased ROS with consequent metabolic reprogramming and mitochondrial dysfunction.
Abstract 13880: Natural Language Processing for Adjudication of Heart Failure Hospitalizations in a Multi-Center Clinical Trial
Authors: Cunningham Jonathan , Singh Pulkit , Reeder Christopher , Claggett Brian , Marti Castellote Pablo-Miki , Lau Emily , Khurshid Shaan , Batra Puneet , Lubitz Steven , Maddah Mahnaz , Philippakis Anthony A , Finn Peter , Desai Akshay S , Ellinor Patrick T , Vardeny Orly , Solomon Scott , Ho Jennifer E
Published: November 2023

Background:
The gold standard for outcome adjudication in clinical trials is chart review by a physician clinical events committee (CEC), which requires substantial time and expertise. Automated adjudication by natural language processing (NLP) may be a more resource-efficient alternative. We previously developed the Community Care Cohort Project (C3PO) NLP model to adjudicate heart failure (HF) hospitalization within one healthcare system.

Aim:
To externally validate the C3PO NLP model against CEC adjudication in the INVESTED trial

Methods:
The INVESTED trial evaluated influenza vaccination in 5260 patients with cardiovascular disease at 157 North American sites. A central CEC of 21 physicians adjudicated the cause of hospitalizations from medical records. We applied the C3PO NLP model to 4060 INVESTED medical record dossiers and evaluated agreement between the NLP and final consensus CEC HF adjudications by kappa statistic, sensitivity and specificity. We fine-tuned the C3PO NLP model (C3PO+INVESTED) and trained a de novo model in half the INVESTED hospitalizations, and evaluated these models in the other half. NLP performance was benchmarked to CEC reviewer inter-rater reproducibility.

Results:
1074 hospitalizations (26%) were considered HF by the CEC. There was high agreement between the C3PO NLP and CEC HF adjudications (agreement 87%, kappa 0.69). C3PO NLP model sensitivity was 94% and specificity was 84%. The fine-tuned C3PO and de novo NLP models demonstrated agreement of 93% and kappa of 0.82 and 0.83, respectively. CEC inter-rater reproducibility was 94% (kappa 0.85).

Conclusion:
In external validation, a single-center NLP model for HF adjudication was accurate relative to the gold-standard CEC in an external multi-center clinical trial. Fine-tuning the model improved agreement to the level of human reproducibility. NLP may improve the efficiency of future multi-center clinical trials by accurately adjudicating clinical events at scale.
Abstract 13882: Myocardial Hypoperfusion in Severe Aortic Stenosis is Reversed by Aortic Valve Replacement
Authors: Thornton George D , Bennett Jonathan B , Nitsche Christian , Gama Francisco , Mravljak Rok , Abiodun Aderonke T , Aziminia Nikoo , Tapia Leire , Knott Kristopher , Pierce Iain , Lloyd Guy , Hughes Alun , Davies Rhodri H , Gonzalez Arantxa , Moon James , Kellman Peter , Treibel Thomas
Published: November 2023

Background:
Myocardial hypoperfusion in severe aortic stenosis (AS) without obstructive coronary disease may be secondary to hemodynamic influences (and therefore readily reversible by aortic valve replacement[AVR]) or structural alterations in the left ventricle (LV) such as increased mass and reduction in capillary density.

Aim:
To evaluate the early effect of AVR on myocardial blood flow (MBF) in patients with severe symptomatic AS without flow-limiting coronary artery disease.

Methods:
Prospective case-control study of severe symptomatic AS without obstructive coronary disease referred for surgical or transcatheter AVR and propensity matched to a control cohort with unobstructed coronary arteries. Patients underwent adenosine stress cardiovascular magnetic resonance at baseline and 8-weeks (median) post-operatively. Histology from 9 myocardial septal biopsies taken at AVR were compared against necropsy controls (n=5).

Results:
52 patients were included; 26 with severe AS (median [IQR] age 71[66-75], 73% male) and 26 age, sex and co-morbidity matched controls. In AS, peak velocity(Vmax) was 4.3m/s[4.1-4.5] and AVA 0.8cm
2
[0.6-0.9]. AS patients had greater LV mass and late gadolinium enhancement. AS patients had lower stress MBF than controls (1.63ml/g/min[1.38-2.08] vs 2.13[1.76-2.52], p=0.003) which increased to 1.97ml/g/min after AVR (p=0.7 post-AVR vs. Controls). This was driven by a 40% increase in subendocardial MBF (1.26ml/g/min[1.18-1.78] to 1.77[1.62-2.32]). Capillary density was reduced almost threefold in AS (495/mm
2
[407-686] vs 1376[1208-1579], p<0.001).

Conclusions:
Severe AS results in subendocardial hypoperfusion which is rapidly improved after AVR. There is a threefold reduction in capillary density, however factors related to elevated afterload (which is reduced by AVR) are the most influential.
Abstract 13890: Global Burden of Myocarditis From 1990 to 2019 and Projections Until 2030
Authors: Qian Juying , Chen Ao , Chen Zhangwei , Ge Junbo
Published: November 2023

Introduction:
Myocarditis remains a major public health challenge worldwide, which might be increasing with the pandemic of coronavirus disease 2019. This study aimed to examine the myocarditis burden at the global level, and predict the future trend until 2030.

Methods:
Incident cases, deaths, disability-adjusted life years (DALYs), and their corresponding age-standardized rates, as metrics of myocarditis burden, were obtained from the Global Burden of Disease Study 2019. The estimated annual percentage changes (EAPCs) were calculated to reveal temporal trends from 1990 to 2019. Bayesian age-period-cohort model was used to make projections.

Results:
Increases were noted in incident cases (62.19%) and deaths (65.4%) of myocarditis, with a slight decrease of DALYs (-0.42%). Age-standardized death rate (ASDR) showed a stable trend over time [EAPC: -0.09, 95% confidence interval (CI): -0.38 to 0.2], decreases were noted in age-standardized incidence rate (ASIR) (EAPC: -0.23, 95% CI: -0.26 to -0.21) and age-standardized DALY rate (EAPC: -1.19, 95% CI: -1.33 to -1.04). Males bore more myocarditis burden than females. Almost a third (29.94%) of myocarditis patients resided in countries with a middle sociodemographic index (SDI). Higher ASIRs were observed in regions with higher SDI levels. People aged less than 20 years in low and low-middle SDI quintiles developed myocarditis and died from it earlier than those in other quintiles. Global ASIR and ASDR were predicted to continuously decrease until 2030.

Conclusions:
These findings suggested considerable heterogeneity in the epidemiologic patterns of myocarditis, guiding the policymakers to formulate optimal strategies and resource allocation for myocarditis.
Abstract 13899: Engineered Tissue Graft Electrically Couples With Swine Host Heart
Authors: Guragain Bijay , Wei Yuhua , Zhang Hanyu , Kahn-Krell Asher , Ye Lei , Walcott Greg , Rogers Jack , Zhang Jianyi J
Published: November 2023

Introduction:
Adult mammalian hearts are unable to replenish myocytes lost in myocardial infarction (MI). Recent therapies that implant myocytes derived from human induced pluripotent stem cells (hiPSC-CMs) have shown structural integration of the graft, improved cardiac function, and reduced scar size. However, to successfully remuscularize the heart, implanted tissue must integrate electrically. Here, we directly image electrical coupling between engineered grafts and the host.

Methods:
We created anterior LV MI in 3 immunosuppressed pigs using ischemia-reperfusion. Cardiac spheroids engineered from hiPSC-CMs were implanted into the border zone right after the procedure. Spheroids were transfected with a calcium indicator (GCaMP6). One week post implantation, the animal was sacrificed, and 0.6 mm thick slices of myocardium containing spheroids were obtained (Fig. A). The slices were stained with a voltage-sensitive dye (VSD) for optical mapping. GCaMP6 and the VSD have different emission spectra allowing electrical activation of the host tissue and spheroids to be imaged independently. The slices were activated with both global field stimuli and focal stimuli applied distant from the spheroids.

Results:
During field stimulation, action potentials in the slice and calcium transients (CaT) in the spheroids were simultaneous. However, during focal pacing, there was propagation across the slices and latency between the pacing pulses and spheroid CaTs (Fig. B, C). This indicates spheroid activation arose from electrical coupling with the host myocardium and not from direct stimulation by the pacing pulse. We observed coupling at 12 spheroid sites in 10 slices. At 6 sites, 1:1 coupling could be maintained at pacing rates up to 4 Hz (Fig. D).

Conclusions:
To our knowledge, this is the first demonstration of swine host myocardium coupling electrically with a human engineered tissue graft. Coupling occurred within 1 week and enabled the host to drive the graft.
Abstract 15602: Impact of COVID-19 on Cardiovascular Outcomes in Patients Hospitalized With Chronic Heart Failure: A Nationwide Propensity-Matched Analysis
Authors: Challa Abhiram , Polana Tejasri , Vasudeva Rhythm , Akkawi Abdul Rahman R , Vindhyal Mohinder Reddy
Published: November 2023

Introduction:
Coronavirus 19 (COVID-19) has rapidly emerged as a major contributor to hospitalizations and readmissions, with growing evidence emphasizing its correlation with adverse outcomes in heart failure (HF). This study aims to investigate the impact of COVID-19 on cardiovascular outcomes in patients hospitalized with HF.

Goals:
To assess the impact COVID-19 on mortality, readmissions, and other cardiovascular outcomes in HF patients.

Methods:
Patients >18 years hospitalized with a diagnosis of chronic HF and COVID-19 were identified in the 2020 National Readmissions Database. Nearest propensity matching (PSM) was conducted using a 1:1 ratio for demographic, social, and clinical variables. PSM was repeated for systolic and diastolic heart failure subgroups. Outcomes with <10 cases were excluded per HCUP rules.

Results:
Amongst the 1,922,680 CHF patients identified, 461 had COVID-19. Baseline characteristics are shown in Table 1. After matching, COVID-19 showed no significant impact on mortality, 30- and 90- day readmissions, acute myocardial infarction, or acute kidney injury (AKI). Interestingly, the subgroup analysis revealed that COVID-19 significantly reduced AKI in diastolic HF (Table 2).

Conclusions:
Patients with COVID-19 hospitalized with HF are not at a higher risk for mortality, readmissions, or other cardiovascular outcomes. Interestingly, a significant reduction in AKI was observed in diastolic HF patients with COVID-19, warranting further investigation.
Abstract 15611: Disparities in Hypertension Control Amidst the Pandemic: A Multi-Year Analysis Using Multiple Hospital Database
Authors: Bolaji Olayiwola , Yun Shaumi , Adabale Olanrewaju , Ouedraogo Faizal , Idowu Abiodun , Nriagu Bede , Evbayekha Endurance O , Sanni Habeeb , Oghoghorie Stanley , Bandaru Revanth Reddy , Dilibe Arthur , Oriaifo Osejie , Shoar Saeed
Published: November 2023

Introduction:
Hypertension, a pervasive global health concern, affects roughly half of US adults and can lead to serious health issues if uncontrolled. This study utilized the Epic Cosmos anonymized database to evaluate blood pressure (BP) control efficacy and related disparities among hypertensive patients from 196 healthcare institutions. Additionally, we explored the pandemic impact on these outcomes.

Hypothesis:
To evaluate blood pressure (BP) control efficacy and related disparities among hypertensive patients from 196 healthcare institutions using the Epic Cosmos anonymized database.

Methods:
Using the Epic Cosmos database, hypertension control rates from 2018 to 2022 were evaluated and stratified by patients' socio-demographic profiles. A multivariable logistic regression analysis identified factors associated with BP control rates.

Results:
In 2022, the study included 13.4 million hypertensive patients aged 18 and older. Of these, 66.0% achieved BP control (BP< 140/90 mm Hg), 31.0% reached stricter control (BP<130/80 mm Hg), and 7.0% had severely uncontrolled hypertension. Control rates were lower among Non-Hispanic Blacks (59.4%) compared to Non-Hispanic Whites (67.5%) with an adjusted odds ratio (AOR) of 0.749 (95% confidence interval (CI): 0.746-0.752). Self-pay patients were less likely to achieve control than insured patients (58.8% vs 66.8%, AOR: 0.79, 95% CI: 0.78-0.80). BP control rates fluctuated from 2018 to 2022, reflecting the pandemic's impact.

Conclusions:
The findings highlight suboptimal hypertension control rates and disparities in the US, emphasizing the need for tailored hypertension management initiatives. These should consider identified disparities and ensure accessibility and cultural sensitivity, aligning with the American Heart Association guidelines.