bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15325: SAH-Responsive Genes Mediate Worsening Metabolic Crosstalk Between Homocysteine-Methionine, Glucose-Related &Lt Lipid Metabolic Systems
Authors: Cueto Ramon , Shen Wen , Liu Lu , Wang Xianwei , Snyder Nathaniel , Yang Xiaofeng , Wang Hong
Published: December 2023

Introduction:
Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease, and other chronic disease. We recently proposed that the homocysteine-methionine (H-M) cycle is a metabolic sensor system responsible for pathological signaling in chronic disease. We identified metabolic worsening crosstalk between HHcy, hyperglycemia and hyperlipidemia in concomitant mouse disease models and in human coronary artery disease.

Research Question:
What is the molecular mechanism mediating worsening metabolic crosstalk in concomitant metabolic disorders?

Methods:
mRNA levels of 324 metabolic genes in three metabolic systems were examined, including 119 for H-M, 95 for glucose-related and 110 genes for lipid in 21 human and 20 mouse organs. Organs were classified based on specific metabolic gene expression. Hcy-metabolites were measured in 6 mouse organs (heart, liver, brain, lung, spleen, and kidney) by LS-ESI-MS/MS. Hcy-metabolites responsive genes were identified by linear regression analyses between metabolites and gene expression levels and used to establish Hcy-metabolites responsive metabolic networks.

Results:
We identified 7 Hcy-, 64 SAH- and 18 SAM:SAH-responsive genes and 3 pathological SAH-responsive cross-talking metabolites (serine, taurine and glycine 3 phosphate). SAH-responsive genes associated with activated upper glycolysis and suppressed lower glycolysis leading to glycolysis-related redox imbalance. A negative correlation between SAH and serine synthesis enzyme PHGDH suggests that increased SAH may suppress serine synthesis which leads to the impairment of transsulfuration, and taurine reduction. SAH-related taurine reduction can further negatively impact cholesterol (CH) degradation. SAH-related upper glycolysis activation leads to the increase of G3P synthesis, which is a substrate for triglyceride (TG) synthesis. In addition, SAH levels may activate fatty acid uptake and β-oxidation leading to elevated acetyl-CoA, CH and TG synthesis.

Conclusion:
H-M cycle is a metabolic sensor system. Production change of serine, taurine and G3P via SAH-responsive metabolic genes can be the key cross-talking metabolites responsible for worsening metabolic crosstalk in metabolic syndrome.
Abstract 15363: Equivalent Total Medical Costs Between Remote Cardiac Rehabilitation and Facility-Based Cardiac Rehabilitation
Authors: Oehler Andrew , Holmstrand Ericka , Zhou Lulu , Harzand Arash , Vathsangam Harshvardhan , Kendall Kellee , Gabriel George , Murali Srinivas
Published: December 2023

Purpose:
Remote cardiac rehabilitation (RCR) represents a promising, non-inferior alternative to facility-based cardiac rehabilitation (FBCR). The comparable cost of RCR in US populations has not been previously studied. The purpose of this prospective, patient-selected study of traditional FBCR vs. a 3
rd
party RCR platform was to assess whether RCR can be administered at comparable cost and clinical efficacy to FBCR.

Methods:
Adult insured patients were eligible for enrollment following an admission for a coronary event. Patients selected either FBCR or Movn RCR, a 12-week telehealth intervention using an app-based platform and internet-capable medical devices. Clinical demographics, intervention adherence, cost-effectiveness, and hospitalizations at 1-year post-enrollment were assessed from the Highmark claims database following propensity matching between groups.

Results:
A total of 260 patients were included, and 171 (65.8%) of those eligible received at least one cardiac rehab session, half of those choosing Movn RCR. Propensity matching produced a sample of 41 matched pairs between FBCR and RCR groups. Movn RCR led to quicker program initiation and higher completion rates (80% vs. 50%). Total medical costs were similar between Movn RCR and FBCR, though tended toward cost savings with Movn RCR ($10,574/patient). Cost of cardiac rehabilitation was lower in those enrolled in Movn RCR ($1377/patient, p=0.002). All-cause and cardiovascular-related hospitalizations or ED visits in the year following enrollment in both groups were similar.

Conclusions:
This pragmatic study of patients after a coronary event led to equivalent total medical costs and lower intervention costs for an RCR platform when compared to traditional FBCR while maintaining similar clinically important outcomes.
Abstract 15365: The Effect of Mobile Phone Messaging in the Reduction of Ambulatory Blood Pressure in Adults: A Systematic Review
Authors: Brouner Michael , Ridgeway Jared , Farris Rex , Sang Charlie , Hansen Ross , Hammock James , Siddiqui Mohammed , Jackson Elizabeth A
Published: December 2023

Introduction:
Ample evidence supports a lower risk for cardiovascular disease (CVD) with controlled blood pressure (BP), yet hypertension (HTN) remains a leading cause of CVD. Mobile health such as text messaging is commonly included in BP management programs; however, the association of texting with BP interventions is less well known. We sought to examine the effectiveness of mobile messaging on BP in adults in the ambulatory setting.

Methods:
In this systematic review, we searched 4 databases from date of inception through February 2023 using search terms (texting, messaging, mobile phone, BP, HTN). After removing duplicate citations, two reviewers independently reviewed the references for eligibility (randomized control trial [RCT], participants > 18 years of age, participants either with elevated BP, and/or a diagnosis of HTN).

Results:
A total of 1,786 RCTs were identified of which 48 met eligibility criteria, for a combined total of 19,720 participants from 21 countries, including 13 US studies. Twenty-seven studies reported significant reductions in BP (systolic, diastolic or both). All three RCTs using texting and pharmacist counseling (n=3) demonstrated significant changes in BP, while 13 of 16 RCTs with texting and provider involvement observed significant improvement in BP. For the studies reporting between group changes in systolic BP from baseline, 7 studies noted significant improvements in BP (Figure 1).

Conclusions:
Despite heterogeneity in study components, we found text messaging when used with other intervention components was associated with BP reductions among adults with HTN. Larger studies using novel designs such as SMART (sequential multiple assignment randomized trials) are warranted to understand efficacy of texting with other intervention components.
Abstract 15366: Quantification of Recent Reporting Rates of Atrioesophageal Fistula After Left Atrial Ablation for the Treatment of Atrial Fibrillation
Authors: Putzel Natalie , Joseph Christopher , Cooper Julie , Sherman Jacob , Lazarus Catherine O , Kulstad Erik B , Daniels James D , Nazari Jose
Published: December 2023

Introduction:
Atrio-esophageal fistulas (AEF) are a feared and fatal complication of left atrial ablation for the treatment of atrial fibrillation (AF). The recent POTTER-AF survey suggests that AEFs continue to occur despite best efforts to prevent them. A quantification of recent incidence rates and outcomes of AEF reported to the Manufacturer and User Facility Device Experience (MAUDE) database of the U.S. FDA may further elucidate trends in this complication.

Research Question(s):
What are the recent trends in reporting rates of AEF, and what are the outcomes?

Purpose:
To quantify the number of AEF reports as well as any reported outcomes of atrioesophageal fistulas and determine any trends over the last 4 years.

Methods:
We reviewed data from the Manufacturer and User Facility Device Experience (MAUDE) database for complications under the category of fistula that occurred over the last 4 years (2019 to 2022 inclusive). Reports were reviewed for any descriptions of outcome, and narratives were compared in an attempt to identify and exclude any duplicate reporting.

Results:
In total, three product codes resulted in 121 reported AEFs. Of these, 50 (41%) were listed as fatal. When provided, the time frame of death ranged from 12 days to several weeks after the index procedure. Product codes reporting AEFs included LPB (88 cases), OAE (22 cases), and OAD (11 cases), with codes representing cardiac ablation catheters and radiofrequency generators. Incidence by year showed a generally increasing trend (21 in 2019, 22 in 2020, 41 in 2021, and 37 in 2022, Figure 1).

Conclusion:
The annual rate of reported AEFs has not decreased over the last 4 years, and instead shows a generally increasing trend. Reported fatality rates remain high at 41%.
Abstract 15376: Candidacy and Fate of Right Heart Failure Patients Undergoing Tricuspid Valve Surgery
Authors: Bauza Karolis , Thuita Lucy , Blackstone Eugene H , Pettersson Gosta B , Elgharably Haytham
Published: December 2023

Objective:
There are no current guidelines for risks and benefits of cardiac surgery for patients with right heart failure (RHF). In this study, we analyzed pre-operative RHF variables aiming to assess candidacy for surgery and impact of tricuspid intervention.

Methods:
We retrospectively identified 522 patients with severe (+3 or more) tricuspid regurgitation (TR) who underwent cardiac surgery between 01/2007 and 01/2014 . The mean follow up was 4.7 years (± 4.3 years). Cluster analysis was performed using preoperative RHF clinical and hemodynamics variables, and outcomes after surgery were assessed.

Results:
Cluster analysis divided the cohort into three distinct clusters representing different phenotypes of patients with RHF-associated TR (cluster 1: 220 patient, cluster 2: 224 patients, cluster 3: 78 patients). Cluster I had highest concomitant left-sided valve procedure (72% mitral valve surgery, p<.0001) with best RV function (fractional area change % 35 ± 13, p=.0002). Cluster II had highest MELD score (14 ± 4, p<.0001), creatinine (1.4 ± 0.6, p<.0001), and worst RV function (fractional area change % 30 ± 12, p=.0002). Cluster III had the most dilated right heart with right atrial area of 42 ± 14 mm, p<.0001 and RV area in diastole 42 ± 10 mm, p<.0001. Survival was best in Cluster I followed by Cluster III while worst in Cluster II (70%, 59%, and 29% at 8-years, respectively), Figure 1. Recurrent TR was highest in Cluster III, followed by Cluster II while least in Cluster I at 10-years (9%, 8%, and 5%, respectively).

Conclusions:
Cluster analysis of RHF identified three distinct groups of patients presenting for cardiac surgery. Pre-operative RV dysfunction was associated with worse clinical outcomes and need careful assessment before surgery. Pre-operative right heart dilation was associated with recurrent TR for which more aggressive tricuspid repair or even replacement might be considered.
Abstract 15381: Clinical Outcomes of Post-Drug-Coated Balloon Angioplasty Dissection in Large De-Novo Coronary Artery Disease
Authors: Yang Cheng , Sui Yong-Gang , Qian Jie
Published: December 2023

Introduction:
Drug-coated balloon (DCB) may be an alternative to stents in the treatment of large native coronary artery disease. However, the complications of acute elastic recoil and coronary dissections confine the practical application of DCB. Little is known about the clinical outcomes of different types of dissection after DCB angioplasty with or without stenting.

Aims:
This study sought to investigate the clinical outcomes of post-DCB dissection in large de novo coronary artery disease.

Methods:
This was a retrospective observational study. A consecutive series of patients with large native coronary artery disease (reference diameter ≥ 3.0 mm) who occurred coronary dissections after the treatment of DCB angioplasty were included. These patients were divided into stented groups and non-stented groups depending on whether bail-out stents were employed. Post-angioplasty coronary artery dissections were classified into type A-F. The cumulative incidence of major adverse cardiac events (MACE) was compared between the two groups.

Results:
Between March 2017 and October 2022, 676 patients with large de novo coronary artery disease developed post-DCB angioplasty dissection, 554 of which treated with DCB only, 122 of which underwent bail-out stent implantation. These dissections were type A (60.5%), B (30.9%), C (6.5%), D (1.9%) and F (0.1%), respectively. During a mean follow-up of 1 year, MACE occurred in 60 patients (9 in the stented group and 51 in the non-stented group; 7.4% vs. 9.2%; p=0.522). For type B dissection, the rate of MACE was similar in the stented group than that in the non-stented group (11.1% vs. 8.2%; p=0.502). For type C dissection, the rate of MACE was numerically higher in the non-stented group than that in the stented group (9.5% vs. 0%; p=0.222).

Conclusions:
For post-DCB angioplasty dissection in large de-novo coronary artery disease, type B dissection requires no bail-out stent implantation and type C dissection deserves further investigation.
Abstract 15391: Five-Year Outcomes in Patients With Acute Coronary Syndrome and Myocardial Revascularization Treated With Prasugrel or Ticagrelor
Authors: Kruger Nils , Krefting Johannes , Sen Partho , Schmieder Raphael , Starnecker Fabian , Dutsch Alexander , Graesser Christian , Grekova Anastasiia , Meyer-Lindemann Ulrike , Storz Theresa , Gueldener Ulrich , Kastrati Adnan , Cassese Salvatore , Schunkert Heribert , von Scheidt Moritz
Published: December 2023

Background:
In patients with acute coronary syndrome (ACS) treated with coronary intervention, potent P2Y12 inhibitors are recommended for 1 year in addition to aspirin. The ISAR-REACT 5 (IR5) trial demonstrated superior efficacy of prasugrel over ticagrelor in reducing the composite of death, myocardial infarction (MI), and stroke at 1 year with comparable bleeding risk. However, long-term data on the relative efficacy of these drugs in real-world settings are lacking.

Methods:
We performed a comprehensive, retrospective cohort study based on German health insurance data. Patients with ACS who underwent percutaneous coronary intervention or coronary artery bypass graft surgery and received either prasugrel or ticagrelor were observed for 5 years. For 36,813 eligible patients, 1:1 propensity score matching was performed based on age, sex, risk factors and type of ACS. Primary endpoint was a composite of death, MI, or stroke. Safety outcome was bleeding.

Results:
After matching, 26,494 patients were included in the study. Mean age was 61.8 years, and 25,3% were female. The risk for the primary endpoint was lower in the prasugrel group compared with ticagrelor at 1 year (hazard ratio (HR): 0.79; 95% confidence interval (CI): 0,73-0.87), and 5 years (HR: 0.84; 95% CI: 0.79-0.89). Prasugrel was statistically superior in reducing individual components of the primary endpoint at 1 and 5 years, respectively. The risk of bleeding was lower in the prasugrel group, though not statistically significant.

Conclusions:
In patients with ACS, prasugrel was associated with a lower risk of the composite of death, MI or stroke, compared with ticagrelor over a 5-year period. While recognizing the limitations associated with secondary data, the strength of these findings lies in the extensive follow-up period involving a large ACS cohort in a real-world setting. The consistency of these results with the IR5 trial reinforces prasugrel's superiority over ticagrelor.
Abstract 15394: Caregivers’ Growing Contributions to Heart Failure Self-Care: An Updated Systematic Review
Authors: Howland Chelsea , Buck Harleah G , Stawnychy Michael A , Aldossary Heba , Cortes Yamnia I , Deberg Jennifer , Durante Angela , Graven Lucinda J , Irani Elliane , Jaboob Saida , Massouh Angela , Da Costa Ferreira Ob Natany , Abshire Saylor Martha , Wion Rachel K , Bidwell Julie T
Published: December 2023

Introduction:
In 2015, a seminal systematic review captured the body of literature surrounding the contributions of family caregivers to heart failure (HF) self-care. Since then, the body of HF caregiving research has expanded, necessitating an updated systematic review to inform research, practice, and policy.
Goals:
To provide an updated systematic review of the empiric literature on informal, unpaid caregivers contributions to HF patients’ self-care.
Research Questions:
1) What specific activities do caregivers of people with HF take part in related to HF self-care?; 2) Have these caregiving activities changed over time?; 3) What are the gaps in the science?

Methods:
The review followed PRISMA guidelines; the protocol was pre-registered in PROSPERO. Comprehensive database search strategies were developed (PubMed, CINAHL, Embase, and Cochrane CENTRAL). The team independently screened and abstracted data; quality was assessed using CASP checklists. Meta-synthesis techniques using critical realist approaches were used to interpret activities, then relationships were analyzed. During data synthesis, activities were benchmarked against the Theory of Self-care in Chronic Illness (TSCI).

Results:
In total, 2154 research reports were identified, 64 of which were eligible for inclusion (2013-2022). Caregiver contributions to HF self-care activities occurred in TCSI domains of self-care maintenance (91%), monitoring (54%), and management (46%). Activities performed directly on or to the patient were reported more frequently than those performed for the patient. Frequently reported activities like transportation and activity of daily living are not included by the TCSI. Gaps due to ambiguous activity descriptions, inadequate caregiving time quantification, and underrepresented monitoring, supportive, and communication activities were elucidated.

Conclusions:
Findings support updating the TSCI to include activities antecedent to HF self-care. Identified gaps highlight the need to define specific caregiving activities, determine caregiver task difficulty and burden, and identify caregiver self-care strategy and education needs. The critical need to expose the hidden work of caregiving is essential to inform policy and practice.
Abstract 15414: Driving Distances and Durations to Nearest Transcatheter Aortic Valve Replacement Center for Medicare Beneficiaries Across Continental United States
Authors: Kapadia Sohum , Shen Miles , Hanna Jonathan , Wheelock Kevin , Dhingra Lovedeep S , Khera Rohan
Published: December 2023

Background:
Transcatheter aortic valve replacement (TAVR) is a rapidly expanding minimally invasive procedure. Although many centers across the continental US offer TAVR, accessibility is a consideration given extensive pre- and post-procedural care. We examined access to TAVR amongst Medicare beneficiaries across the US.

Methods:
We identified TAVR providers based on clinician billing records for CPT codes 33361-33369 in the 2020 Medicare provider dataset, available from Centers for Medicare and Medicaid Services. Residential and practice zip codes were identified from national geopolitical data. Across the US, haversine spherical pairwise straight-line distances were computed between all residential and provider zip codes. Based on proximate residential and provider zip code pairs, we used the Google Distance Matrix API to calculate average driving distance and travel time to providers for all residential zip codes.

Results:
There were 936 TAVR providers across 409 US zip codes, against a total of 29,089 residential US zip codes. Wyoming had no TAVR providers, while Florida had the most (n=69). Median travel duration (minutes) was lowest in the District of Columbia (20 min) and greatest in Montana (282 min). The median [IQR] traveling distance (miles) to the closest TAVR site was lowest in the Northeast (30 [13-55]) and greatest for the West (84 [29-151]), with the Midwest (46 [24-74]) and South (57 [26-90] in between (p < 0.001). The median [IQR] traveling duration (minutes) showed similar trends to distance (Northeast: (38 [22-66]); Midwest: (52 [30-80]); South: (64 [34-97]); West: 91 [40-158]); p < 0.001);
Figure 1
). 75% of zip codes travel a minimum of 30 minutes to the nearest TAVR provider.

Conclusions:
There are significant regional differences for TAVR accessibility in the US, with extended travel times of over 1 hour for 1 in 2 US zip codes and over 2 hours for 1 in 7 US zip codes to receive standard care.
Abstract 15430: Dramatic Reduction in Lipoprotein(a) With Immunosuppressant, Anti-Inflammatory, and Antimicrobial Therapy in a Patient With Multiple Inflammatory Diseases
Authors: Mazdeyasnan Donya , Wilkinson Michael J
Published: December 2023

Background:
Lipoprotein(a) (Lp(a)) is a potent, causative risk factor for ASCVD. Patients with inflammatory and autoimmune diseases are also at increased ASCVD risk. There is a complex, incompletely understood relationship between inflammation and Lp(a), including observations that IL-6 induces
LPA
gene expression. We present a unique case of dramatic Lp(a) lowering occurring with a combination of immunosuppressing, anti-inflammatory, and antimicrobial therapies.

Case:
A 50-year-old Black woman was referred to Lipid Clinic for Lp(a) of 138 mg/dL. Medical history included Crohn’s disease, total colectomy and end ileostomy, seronegative inflammatory polyarthropathy with psoriatic arthritis, and reactive neutrophilic dermatosis with suspected bowel-associated dermatitis-arthritis syndrome (BADAS). CT coronary calcium score was 0 Agatston units, but plaque was visible in her right coronary artery below the threshold for quantification. With rosuvastatin 5mg daily (which can increase Lp(a)), she experienced a ~25% reduction in LDL-C (baseline 102 mg/dL). She was not treated with niacin or PCSK9 inhibitors. Over the course of ~2.5 years, as the patient experienced BADAS flares she received extensive immunosuppressing, anti-inflammatory, and antimicrobial treatment including adalimumab (TNF-alpha inhibitor), sulfasalazine, dapsone, and doxycycline, and her Lp(a) decreased from 138 mg/dL to a low of 48 mg/dL (65% reduction) (Figure).

Conclusion:
Previous studies have shown that certain immunosuppressing therapies may lower Lp(a), and in this unique case we observed a dramatic reduction in Lp(a) during treatment with a complex regimen of immunosuppressing, anti-inflammatory, and antimicrobial therapies in a patient experiencing frequent flares of inflammatory diseases. The relationship between Lp(a), systemic inflammation, and the potential effects of anti-inflammatory and immunosuppressive therapies on Lp(a) deserves further study.
Abstract 15459: Statin Twitter: Human and "Bot" Contributions, 2010-2022
Authors: Slavin Samuel D , Berman Adam , Beam Andrew , Navar Ann Marie , Mittleman Murray A
Published: December 2023

Background:
Half of patients with ASCVD do not take statin medications despite proven efficacy and safety. Misinformation about statins drives skepticism about their use. Social media “bots” are known to proliferate misinformation, but involvement in statin-related discourse is unknown.

Objectives:
1) to examine temporal trends in volume and sentiment of statin-related Twitter posts (tweets); 2) to compare statin-related content generated by humans and bots

Methods:
We queried Twitter for all tweets with statin-related terms from 2010-2022. We used a machine learning-derived classifier to determine tweet authorship as bot, human, or intermediate, and natural language processing to assign a sentiment score to each tweet. Manual qualitative analysis was performed on a randomly selected sample of all tweets and highly influential tweets to quantify statin skepticism.

Results:
We identified 1,155,735 original tweets (excluding retweets) with statin-related terms, the most common being “statin” (n=832,627, 72%) and “Lipitor” (n=197,015, 17%). Bots produced 333,689 (29%), humans produced 699,876 (61%), and intermediate accounts produced 104,966 (9.1%). Over the study period, the proportion of bot tweets decreased from 48% to 11%, human tweets increased from 44% to 80%, and intermediate tweets decreased from 7.7% to 6.7%. The proportion of negative sentiment tweets increased from 28% to 43% for bots, 31% to 38% for humans, and 29% to 40% for intermediate accounts. Including retweets, negative sentiment increased from 30% to 45% across all tweets. In a qualitative analysis of highly influential tweets, statin skepticism increased from 7% to 29% for bots and 25% to 36% for humans.

Conclusions:
Since 2010, humans have overtaken bots as generators of statin-related content on Twitter. Negative sentiment and statin skepticism have increased, especially among highly influential tweets. Misinformation interventions should focus on human users and influential bots.
Abstract 15474: Factors Associated With Shock at Presentation for Patients With Kawasaki Disease versus Multisystem Inflammatory Syndrome in Children Associated With COVID-19
Authors: Jain Supriya S , Lowndes Robert , grcic michelle , Bashir Ayisha , Garrido Luis M , Dahdah Nagib , Misra Nilanjana , Pagano Joseph J , Maksymiuk Victoria , Jone Pei-Ni , Prasad Deepa , Harris Tyler , Szmuszkovicz Jacqueline R , Barnes Benjamin , Mondal Tapas K , Khare Manaswitha , Truong Dongngan , Farid Pedrom , Manlhiot Cedric , McCrindle Brian W
Published: December 2023

Background:
Comparisons between Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) have been critiqued, with suggestions that KD Shock Syndrome (KDSS) patients may be a more valid comparison. We compared contemporaneous KD and MIS-C patients, both with and without shock at presentation.

Methods:
The International KD Registry enrolled 2144 patients with either KD (site diagnosis confirmed by AHA criteria) or MIS-C (site diagnosis confirmed by CDC criteria) from 40 sites in 7 countries from 01/2020 to 01/2023. Data collected included demographics, clinical features and presentation, management, laboratory values, and outcomes, and diagnosis/shock groups were compared.

Results:
Shock at presentation was noted for 19 of 672 (2.8%) KD patients and 653 of 1472 (38%; p<0.001) MIS-C patients. For both groups, shock patients were significantly more likely to be admitted to ICU, receive inotropes, and have cardiac arrest or arrhythmia. Groups did not differ by sex, but MIS-C patients and shock patients were older. While MIS-C shock patients were less likely to be White, KD shock and MIS-C shock patients more likely to be Black. For inflammatory markers, while shock patients in both groups had higher CRP and ferritin compared to non-shock patients, ESR was similar in both groups to non-shock patients, and higher WBC was only noted for MIS-C shock versus MIS-C non-shock patients. KD shock patients had similar values to MIS-C shock patients, with the exception of lower ferritin. Shock patients had higher NTproBNP (both diagnoses) and Troponin I (MIS-C only). Shock patients had lower LV ejection fraction, more so for MIS-C patients (
Figure A
). KD shock patients had higher max coronary artery Z scores versus MIS-C patients (
Figure B
).

Conclusions:
KD shock patients are more similar to MIS-C patients, particularly those with shock. Shock was associated with worse coronary artery involvement for KD patients, and worse LV dysfunction for both MIS-C and KD.
Abstract 15479: High Output Cardiac Failure Associated With Arteriovenous Fistula
Authors: Quintero Bisono Janina , George Bistees , Ormachea Kori
Published: December 2023

Introduction:
High output heart failure (HOHF) secondary to arteriovenous fistula (AVF) is known. However, having a high index of suspicion for the latter when encountering diuretic resistance in patients with a remote history of hemodialysis is key.

Case
A 68-year-old female with a history of kidney transplant in 2012 with no recent dialysis, hypertension, hyperlipidemia, pulmonary hypertension, heart failure with reduced ejection fraction, and atrial fibrillation presented with decompensated heart failure and acute kidney injury (AKI). Physical exam was remarkable for anasarca, and no apparent fistulas were noted. She was started on milrinone and furosemide drips.

Clinical decision making
Initial transthoracic echocardiogram (TTE) revealed an ejection fraction (EF) of 20%, which declined from 35%, along with new mitral and tricuspid regurgitation. Her hospitalization was complicated by altered mental status, worsening AKI requiring hemodialysis, atrial fibrillation with rapid ventricular response, and resistance to multiple diuretics and after-load reduction combinations. Diuretics and inotropic support were discontinued due to worsening clinical status. Given concerns for valvular disease, a transesophageal echocardiogram was obtained, confirming moderate to severe mitral and tricuspid valve regurgitation, bi-atrial enlargement, and reduced biventricular function. However, the patient was not clinically optimized for Mitra-clip. Further hemodynamics and volume status assessment with RHC revealed a mean PAP 44, PCWP 26, and CO 11 L/min. RHC results raised suspicion for HOHF. Interestingly, the patient was noted to have a right inguinal surgical scar with a palpable thrill, and an arteriovenous graft duplex revealed high volume flow. The patient underwent ligation of the right inguinal fistula. Repeat TTE two weeks post AVF ligation showed EF of 40% and improved functional mitral and tricuspid valve regurgitation. The patient ultimately was taken off hemodialysis and had clinically improved heart failure. GDMT was optimized, and outpatient evaluation for mitral valve intervention was scheduled.

Conclusion
Longstanding AVF can cause HOHF. Early index of suspicion is warranted for AVF ligation as it results in rapid EF recovery.
Abstract 15483: Mitoquinone Pretreatment Mitigates Dox-induced Systolic Dysfunction in Isolated Rat Hearts
Authors: Melnik Juliet , Dawes Kimberly , Lyons Meagan , Ghasb Gabby , Amora Jonathan , Young Lindon , Barsotti Robert , CHEN Qian
Published: December 2023

Background:
Doxorubicin (DOX) is a common and effective chemotherapeutic agent that can exert cardiotoxicity by inducing oxidative stress in mitochondria, compromising mitochondrial function, and inducing apoptosis. Currently, there is no treatment that targets this mechanism. We previously found that pretreatment with higher concentrations of mitoquinone (MQ), a mitochondrial antioxidant, exerts cardioprotection against DOX in myoblast H9C2 cells.

Hypothesis:
We hypothesize that MQ pretreatment would preserve cardiac function against DOX in isolated rat hearts.

Methods:
Cardiac parameters (heart rate (HR) and left ventricular end systolic pressure (LVESP)) were monitored before and after 60 min infusion of DOX, MQ, or DOX with MQ pretreatment (10-15 min) in a Langendorff preparation of male SD rat hearts. TUNEL assay was conducted on heart tissue slides to evaluate apoptosis. The ratio between the final and initial cardiac parameters was calculated and compared among experimental groups.

Results:
Higher dose DOX (25 μM, n=5) induced a higher reduction in the ratios of LVESP, to 39±5% than lower dose DOX infusion (20 μM, n=3; 74±3%). DOX had no effects on HR. A 60-minute perfusion of higher doses of MQ (1-5 μM, n=7) unexpectedly reduced the ratios of LVESP and HR to 73±12% and 66±5%, respectively. Higher dose MQ (1-2.5 μM, n=6) pretreatment showed similar improvement of LVESP ratio (68±9%) to lower dose MQ (0.25-0.5 μM, n=6; 71±11%). TUNEL assay showed that higher dose DOX caused a higher rate of apoptosis (number of TUNEL-positive nuclei) (326.3±6.4. n=3) than lower dose (214±29.5, n=3). Pretreatment with higher dose MQ prior to DOX 25 μM infusion resulted in a notable reduction of apoptosis (60.3±5, n=6) compared to DOX alone, while lower dose pretreatment reduced apoptosis to 70.5± 0.5 (n=4).

Conclusion:
This study suggests that infusion of DOX into the heart acutely attenuated cardiac systolic function accompanied with higher apoptotic cell damage. Although prolonged administration of higher doses of MQ suppressed cardiac function, MQ pretreatment for 10-15 minutes mitigated DOX-induced systolic dysfunction and reduced cardiomyocyte apoptosis. In summary, MQ pretreatment may mitigate DOX-induced cardiac damage.
Abstract 15490: NIL10: A Novel Nanotechnological Compound to Prevent Monocyte Infiltration and Adverse Cardiac Remodeling in a Porcine Model of Myocardial Ischaemia-Reperfusion
Authors: Tesoro Laura , Jimenez Beatriz , Ramirez-Carracedo Rafael , Botana Laura , Hernandez Navarro Ignacio , Diez Mata Javier , Alcharani Nunzio , Gonzalez-Cucharero Claudia , Saura Marta , Zamorano Jose , Zaragoza Carlos
Published: December 2023

Introduction:
Adverse cardiac remodeling following acute myocardial infarction (AMI) depends on how promptly the phagocytic-nuclear system responds. Among strategies to limit the inflammatory response, we have developed a nanoparticle (NIL10) which binds to IL-10 receptor (IL-10R) in-vitro and promotes macrophage polarization towards a resolutive phenotype in animal models of myocardial ischemia-reperfusion (I/R). However, its therapeutic use still depends on understanding its ability to regulate monocyte recruitment.

Hypothesis:
Targeting the IL-10R in circulating monocytes may represent a new therapeutic approach to improve cardiac function in patients undergoing AMI.
Objective:
To explore the molecular mechanisms leading to the inhibition of monocyte recruitment by NIL10 in pigs undergoing cardiac I/R.

Methods:
By using a porcine model of myocardial I/R, we arranged the following groups: (1) control group (2) intravenous administration (IV) 1 mg/kg NIL10, (3) IV of 4x10
5
isolated monocytes from group 2, (4) IV of 4x10
5
isolated monocytes from group 1 and then incubated with NIL10 (A).

Results:
Groups 2-4 exhibited better cardiac function compared to group 1 (B), which resulted in a decrease in myocardial fibrosis (C), along with a reduction of circulating CCR2+ monocytes (D) and a decrease in classical-monocyte infiltration, as shown by a reduction of CCR2+ macrophages in the necrotic area of the heart (E). As a result, CCL2 plasma expression, a functional ligand of CCR2, was decreased by day 7 post-I/R (F) in contrast to the necrotic tissue expression profile in which we detected large amounts of CCL2 (G) and STAT3 activation, indicative of IL10R activity (H).

Conclusion:
In addition to macrophage polarization, NIL10 induces cardiac protection by limiting classical monocyte infiltration after myocardial I/R, which opens a new window for using, in combination with endogenous monocyte therapy, to treat AMI.
Abstract 15495: Serial Measurement of Vascular Endothelial Growth Factor-D in Heart Failure: The PREHOSP-CHF Study
Authors: Iguchi Moritake , Wada Hiromichi , Shinozaki Tsuyoshi , suzuki masahiro , Ajiro Yoichi , Matsuda Morihiro , Koike Akihiro , Koizumi Tomomi , shimizu masatoshi , Ono Yujiro , Takenaka Takashi , Sakagami Satoru , Morita Yukiko , Fujimoto Kazuteru , Yonezawa Kazuya , Yoshida Kazuro , Ninomiya Akiyo , Nakamura Toshihiro , FUNADA JUNICHI , Kajikawa Yutaka , Oishi Yoishifumi , Kato Toru , Kotani Kazuhiko , Abe Mitsuru , Akao Masaharu , Hasegawa Koji
Published: December 2023

Background:
Vascular endothelial growth factor-D (VEGF-D) is a secreted glycoprotein that can act as lymphangiogenic and angiogenic growth factors. We recently reported that VEGF-D appeared to be a prognostic marker for major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death or heart failure hospitalization (HF), in patients with HF. However, the prognostic value of changes of VEGF-D is unknown.

Methods:
The PREHOSP-CHF study is a nationwide prospective survey of patients with HF in Japan. Serum VEGF-D levels were measured in 203 patients (mean age, 75 years; male, 62%; mean ejection fraction, 45%) at both baseline and 6-month follow-up. We set the cut-off level of VEGF-D as 366 pg/ml, based on the ROC analysis of the entire cohort of the PREHOSP-CHF study. We defined increased VEGF-D as transition from low VEGF-D to high VEGF-D and decreased VEGF-D as transition from high to low. We investigated the association of changes of VEGF-D levels with the incidence of MACE after 6 months.

Results:
Mean VEGF-D levels at baseline and 6-month follow-up were 449±199 pg/ml and 519±230 pg/ml, respectively. During the 2-year follow-up, 18 patients developed MACE before 6-month follow-up, and 42 patients developed MACE after 6-month follow up. Based on levels of VEGF-D at baseline, patients with high VEGF-D showed significantly higher incidence of MACE than those without. After excluding the patients developed MACE before 6-month follow-up, 11 of 105 patients with high VEGF-D moved to the low VEGF-D group at 6-month follow-up, and 34 of 78 patients with low VEGF-D moved to the high VEGF-D group. Landmark analysis after 6 months showed that incidence of MACE was significantly higher in patients with increased VEGF-D than those without in the low VEGF-D group, and tended to be lower in patients with deceased VEGF-D than those without in the high VEGF-D group. After adjustment for ejection fraction, N-terminal B-type natriuretic peptide levels, and VEGF-D levels at baseline, increased VEGF-D were also significantly associated with the incidence of MACE after 6 months (hazard ratio per 10 pg/ml increase, 1.02; 95% confidence interval 1.00-1.03; P=0.04).

Conclusions:
In patients with HF, changes in VEGF-D might serve as a prognostic marker for MACE.
Abstract 15499: Biochemical and Genetic Newborn Screening for Familial Hypercholesterolemia
Authors: Peterson Amy L , Shao Xiangqiang , Zhang Xiao , Lasarev Michael , Benoy Megan , Held Patrice , Horner Vanessa
Published: December 2023

Introduction:
Familial Hypercholesterolemia (FH) causes elevated low-density lipoprotein cholesterol (LDL-C) and premature atherosclerosis. Despite guidelines, universal screening rates remain low. Newborn screening could increase FH diagnostic rates.

Hypothesis:
FH can be diagnosed from newborn dried blood spots for LDL-C, total cholesterol (TC), and apolipoprotein B (apoB), followed by selective genetic testing to identify pathogenic and likely pathogenic variants causing FH.

Methods:
De-identified, residual newborn screening dried blood spots were analyzed for LDL-C, TC, and apoB with results expressed as multiples of the median (MoM). Mahalanobis distance (measuring MoM different from 1) was computed and the top 8% of distances selected for genetic testing (panel including
LDLR
,
APOB
,
PCSK9
,
LDLRAP1
,
APOE
,
LIPA
,
ABCG5
, and
ABCG8
).

Results:
A total of 10,004 specimens had biochemical testing, with 768 specimens selected for genetic testing. In total 15 variants were identified, 11 pathogenic and 4 likely pathogenic (Table 1). Composite Mahalanobis distance from LDL-C and apoB identified the most variants, followed by apoB alone and then LDL-C alone. TC alone identified the fewest number of variants (Table 2).

Conclusions:
Testing newborn dried blood spots with biochemical and reflex genetic testing is feasible to detect FH. Genetic testing of about 8% of samples identified 1 in 667 newborns with FH, but more extensive genetic testing would likely detect more variants. Prospective studies are needed to correlate newborn results with LDL-C levels later in childhood.
Abstract 15510: Generation of the Cardiac Valve Lineage From Human Pluripotent Stem Cells
Authors: Mazine Amine , Mikryukov Alexander , Fernandes Ian , Liu Clifford , Jahangiri Soheil , Martin Marcy , Gähwiler Eric K , Gomez Juliana , Latifi Neda , Laflamme Michael A , Simmons Craig A , Hoerstrup Simon P , Emmert Maximilian Y , Gelb Bruce D , Gu Mingxia , Keller Gordon M
Published: December 2023

Background:
Heart valves are living structures whose sophisticated functions are mediated by a specialized population of valvular interstitial cells (VICs). Given their central role in valve homeostasis, VICs represent a promising cell population for studying valve diseases and developing novel therapies to treat them. Herein, we describe the generation of VIC-like cells from human pluripotent stem cells (hPSCs).

Methods and Results:
Using a previously established protocol, we first generated endocardial cells from cardiovascular mesoderm. Within this endocardial population, we identified a subset of cells — marked by the expression of PDGFRβ — that express valvular endocardial cell (VEC) markers and demonstrate VEC-like functional properties, namely the ability to generate calcium transients in response to ATP and the ability to undergo endothelial-to-mesenchymal transition (EndoMT). Through stage-specific manipulation of developmental signaling pathways, we established a protocol that promotes the development of VIC-like cells from these hPSC-derived VEC progenitors (Figure 1A). The cells thus generated transcriptionally matched primary human fetal VICs by scRNAseq. When embedded in a tissue-engineered scaffold, hPSC-VICs secreted collagen and glycosaminoglycans, and demonstrated compact tissue organization analogous to that of native valve leaflets (Figure 1B, C). Finally, we show that VICs generated from an hPSC line with a Noonan syndrome mutation displayed excessive endocardial cell proliferation, diminished EndoMT, and dysregulated pERK activity, recapitulating key aspects of the disease.

Conclusions:
Together, the findings presented in this report provide a reproducible method for the scaled generation of
bona fide
VICs from hPSCs. The generation of hPSC-VICs addresses an important gap in the field and provides a platform to study valvulogenesis and heart valve disease, as well as a novel avenue for heart valve tissue engineering.
Abstract 15537: The Role of Liver Epsins in Nonalcoholic Steatohepatitis
Authors: Zhu Bo , Wu Hao , Wang Beibei , Lu Yao Wei , Chen Hong
Published: December 2023

Introduction:
Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that is associated with high risks of cardiovascular diseases. Epsin is an evolutionarily conserved protein family that is involved in clathrin-mediated endocytosis. We found that both Epsin1/2 expressions in the liver are significantly up-regulated by the Western Diet (WD) induced NASH mice model, as well as in the liver biopsy of NASH patients.

Hypothesis:
We hypothesize that the expressions of Epsin1 and Epsin2 in the liver are required for NASH progression.

Methods:
We conditionally deleted Epsin1/2 using Albumin-Cre (Liver-DKO). We then induced a mouse model of NASH by feeding both WT and Liver-DKO mice a WD for 52 weeks. We used single cell multiome, combined with molecular approaches to study the mechanisms. We tested a strategy to deliver Epsin1/2 siRNAs encapsulated nanoparticles (NPs) targeting the liver via intravenous injection to treat diet induced NASH in mice.

Results:
We found WD-fed Liver-DKO mice have significant reductions in hepatic fibrosis formation and less lipid accumulation, and this was associated with better glucose and insulin tolerance, as well as lower serum aspartate transaminase (AST) and alanine aminotransferase (ALT) compared with WD-fed WT mice. Through analysis of the single cell multiome from the WT and Liver-DKO livers, we found more Kupffer cell in WT NASH mice compared with DKO. Interestingly, monocyte-derived inflammantory Kupffer cell (KCs) are enriched in WD-fed WT mice, however, embryonic-derived KCs are the enriched in liver DKO, and associate with dramatically reduced total KCs population. We also found that HNF4a was dramatically reduced in WD-fed WT mice, but its expression was preserved in WD-fed Liver-DKO mice, suggesting the loss of hepatocyte identity was inhibited by Epsins deletion. Therapeutically, we found significant resolution of hepatic fibrosis after knockdown of Epsin1/2 siRNA NP treatment.

Conclusions:
Liver specific deletion of Epsin1/2 significantly inhibits NASH progression by suppression of inflammation that protects hepatocytes from severe chronic injury. Our preclinical data suggests specially targeting Epsin1 and Epsin2 in the liver could be a promising therapeutic strategy for NASH treatment.
Abstract 15540: Comparative Outcomes of Femoropopliteal Intravascular Ultrasound Interventions: A Report From the XLPAD Registry
Authors: Fernandez Vazquez David , Weideman Sarah , Bruneman Blake , NANJUNDAPPA Aravinda , Metzger Christopher , sayfo sameh , Rosol Zachary , Tsai Shirling , Shishehbor Mehdi H , Banerjee Subhash
Published: December 2023

Background:
Intravascular ultrasound (IVUS) during peripheral artery intervention is being increasingly used, however there is limited real-world procedural and outcomes data.

Methods:
We examined 4847 patients from the XLPAD Registry (NCT01904851) from 2006-2021 that underwent femoropopliteal (FP) endovascular intervention. The primary outcome was the incidence of major adverse limb events (MALE), which includes death, clinically driven revascularization, amputation, myocardial infarction (MI), and stroke. Comparative analyses were done between patients with IVUS and no IVUS interventions.

Results:
322 (6.6%) patients underwent an IVUS guided FP intervention and 4525 without. Mean age 67, predominantly men (83% IVUS-group vs. 71% non-IVUS, p<0.0001) and Caucasian (71% vs. 69%, p=NS). IVUS patients had worse risk profiles, with more smokers (59% vs. 47 %, p<0.0001), heart failure (20% vs. 14%, p=0.006) and prior-MI (31% vs. 22%, p<0.0001), and similar proportion of hypertensives, diabetics, dyslipidemics, or those with chronic kidney disease. IVUS patients had more multivessel intervention (2.4 vs. 1.9 lesions, p<0.0001), SFA being the most common artery, followed by the popliteal artery in both groups. Balloon angioplasty was more common in the non-IVUS group (68% vs. 75%, p=0.005), whereas drug coated balloons (19% vs. 12%, p=0.005), drug-eluting stents (15 vs. 9%, p=0.001) and vascular mimetic stents (13 vs. 4%, p<0.0001) were more frequent in the IVUS patients. Fluoroscopy time was longer in IVUS patients (35 min vs 30 min., p=0.005) with similar rates of procedural (90% vs. 93, p=NS) and technical success (94% vs. 95%, p=NS). There were no differences in peri-procedural complications, or 12-month MALE (21% vs. 20%, p=NS). Only death from any cause was significantly higher in the non-IVUS group (0.7 vs 3.0%, p=0.017).

Conclusion:
IVUS use is under 7% of all FP interventions in the XLPAD registry with IVUS guidance is used in patients with more adverse clinical risk profile, however with no difference in technical, procedural success and 12-month MALE events.