bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15463: Association of Coronary Plaque Morphology With Inflammatory Biomarkers and Target Lesion Revascularization in Patients With Stable Angina Pectoris
Authors: Saiin Kohei , Konishi Takao , Kazui Sho , Yasui Yutaro , Takahashi Yuki , Naito Seiichiro , Takenaka Sakae , Mizuguchi Yoshifumi , Tada Atsushi , Kobayashi Yuta , Kato Yoshiya , Omote Kazunori , Sato Takuma , Kamiya Kiwamu , Nagai Toshiyuki , Tanaka Shinya , Anzai Toshihisa
Published: June 2023

Background:
In many countries, coronary artery disease (CAD) is one of the most common causes of death, and stable angina pectoris (SAP) is the most common initial symptomatic presentation. Despite the contemporary evolution of percutaneous coronary intervention (PCI) using drug-eluting stenting and a drug-coated balloon, restenosis and repeat revascularization still remain major concerns and are limiting the efficacy of PCI in patients with SAP . The characteristics of high-risk coronary atherosclerosis evaluated by optical coherence tomography (OCT) were suggested to have a prognostic role. Inflammatory biomarkers may be related to coronary artery disease severity. Accordingly, this study aimed to investigate the association of high-risk coronary plaque morphologies detected by OCT with circulating inflammatory biomarkers and adverse cardiovascular events.

Methods:
We prospectively analyzed the data of 30 consecutive patients with stable angina pectoris (SAP) who underwent percutaneous coronary intervention (PCI) using optical coherence tomography (OCT) between April 2020 and November 2020 in our university hospital. Inflammatory biomarker measurement and an OCT analysis focused on high-risk coronary plaque features were performed. Based on the coronary plaque risk score (CPRS), patients were defined as having a low CPRS (CPRS ≤3) or high CPRS (CPRS ≥4). The primary outcome was target lesion revascularization (TLR).

Results:
TLR occurred in 6 patients (20%) within 15 months after PCI. A high CPRS assessed by OCT was directly correlated to TLR (P=0.029). In a logistic regression analysis, the CPRS was associated with TLR (odds ratio, 10.0; 95% confidence interval, 1.34-74.5). Among inflammatory biomarkers, MCP-1 was significantly correlated with the CPRS (P=0.020).

Conclusions:
In patients with SAP, the CPRS may be a potential surrogate index for predicting TLR. MCP-1 might be useful for detecting high-risk coronary atherosclerosis.
Abstract 15501: Rare Genomic Copy Number Variants Implicate New Candidate Genes for Bicuspid Aortic Valve
Authors: Carlisle Steven G , Albasha Hasan , Michelena Hector I , Sabate-Rotes Anna , Bianco Lisa , DeBacker Julie , Muino Mosquera Laura , Yetman Angela T , Bissell Malenka , Andreassi Maria Grazia , Foffa Ilenia , Hui Dawn , Caffarelli Anthony D , Kim Yuli Y , Guo Dongchuan , Citro Rodolfo , De Marco Margot , Tretter Justin ,   EBAV Investigators,   BAVCON Investigators, Hanchard Neil A , Belmont John W , McBride Kim L , Body Simon C , Prakash Siddharth K
Published: June 2023

Introduction:
Bicuspid Aortic Valve (BAV), the most common adult congenital heart defect, is a major cause of aortic insufficiency or stenosis requiring valve replacement and thoracic aortic aneurysms predisposing to acute aortic dissections. The spectrum of BAV ranges from early onset valve and aortic complications to sporadic late onset disease. We determined the frequency and gene content of rare genomic copy number variants (CNVs) in isolated BAV cases.

Methods:
We performed genome-wide SNP microarray analysis of familial BAV cases with early onset complications in the UTHealth BAV Research Registry (EBAV, n=394) and elderly probands from the International BAV Consortium (BAVCON, n=4216). CNVs were detected in Illumina genotypes using the PennCNV, QuantiSNP and cnvPartition algorithms. BAV cases were compared to 16,576 controls without known cardiovascular disease from the Database of Genotypes and Phenotypes. Only CNV calls with >6 consecutive variants, >20 kb in length, identified by at least two algorithms and intersected with known genes were included. For comparison, we assessed a cohort with left ventricular outflow tract obstructive lesions including BAV (LVOTO, n=1561) using identical methods. CNV burden and associations were tested using PLINK.

Results:
We identified 84 large recurrent CNVs in BAV cases that are absent or rare (<0.1%) in controls. 34 rare CNVs overlap between BAV and LVOTO cases and involve candidate genes that interact with each other during heart development. The largest and most prevalent of the recurrent CNVs are 8p23 duplications involving
GATA4
(OR 340, CI: 42-2700). CNVs of genes that cause BAV when mutated were significantly enriched in cases (n=135,
P
=1x10
-27
). The overall burden of rare genic CNVs, specifically large deletions, was also increased in BAV cases (empiric
P
< 1x10
-5
) and was higher in younger EBAV cases than in older BAVCON cases.

Conclusion:
We identified likely pathogenic CNVs in more than 10% of BAV cases, implicating alterations of candidate genes at these loci in the pathogenesis of BAV.
Abstract 15506: Optical Mapping in Atrial Engineered Heart Tissues Reveals Proarrhythmic Potential of the Anti-AF Agent Vernakalant
Authors: Gokhan Ilhan , Frimpong Afia Sarpong , Cacheux Marine , Campbell Stuart G , Akar Fadi G
Published: June 2023

Pharmacotherapy for atrial fibrillation (AF) is confounded by ventricular proarrhythmia. Vernakalant (VER) belongs to a class of atrial selective channel blockers developed in attempts to convert AF safely. Yet, robust analysis of the effects of VER in human based tissues has not been performed. We hypothesized that engineered heart tissues (EHT) composed of atrial (A) or ventricular (V) human iPSCs would provide a robust platform for quantitative analysis of chamber specific electrophysiological (EP) effects of VER.

Methods:
iPSCs were differentiated into cardiomyocytes using biphasic Wnt signaling, insulin, and lactate purification. Atrial-like myocytes were enriched by adding 0.75 μM retinoic acid on days 4-6 to promote atrial gene expression and specification. Myocytes were seeded onto cryosectioned, laser cut and decellularized myocardial tissues and cultured under isometric conditions. EHTs were stained with high dose, water soluble di-2-ANEPEQ to enhance signal-to-noise while avoiding toxicity.

Results:
Staining with 25 μM di-2-ANEPEQ provided high fidelity optical AP signals that allowed comprehensive characterization of the EP substrate. A-EHT exhibited significantly shorter AP durations than V-EHT reflecting greater repolarizing drive (APD80, 180 ms vs 367 ms; p < 0.0001, n = 4-5). Consistent with its role as an atrial-selective blocker, VER increased APD80 only in A-EHTs (180 ms vs 258 ms, p = 0.0027, n = 5). This beneficial property for combatting AF was countered by marked slowing of A-EHT conduction and AP upstroke velocity (20.6 cm/s vs 11.7 cm/s, p = 0.027, n = 5).

Conclusions:
Optical mapping of chamber specific EHTs confirms atrial specific nature of VER as an atrial repolarization prolonging agent but raises unexpected concerns regarding potential proarrhythmic toxicity related to atrial conduction slowing.
Abstract 15519: Site- and Cell-Selective Treatment of Atherosclerosis Using a Combination of RNA Therapeutic Approaches
Authors: Hetherington Isabella , VanWye Jeffrey , Wickramage Ishani , Hortu Ismet , Totary-jain Hana
Published: June 2023

Atherosclerotic plaque formation in the arteries underlies acute coronary syndromes (ACS); therapies to treat atherosclerosis that are both site- and cell-selective are not available. The CANTOS clinical trial demonstrated the benefits of targeting inflammation to reduce adverse cardiac events, but the systemic immune suppression increased incidence of sepsis or death caused by infections, highlighting the need for local inflammation inhibition. To assess the local chronic inflammatory state associated with atherosclerotic plaques, coronary arteries were isolated from non-transplantable human hearts (
Fig. A)
from donors ranging in age from 6-months to 72 years old. Donors aged 51-72 had various conditions including hypertension, hypercholesterolemia, and atherosclerosis. Strikingly, qPCR analysis showed an increase in interleukin 1 beta (IL-1β) mRNA levels corresponding to increasing age of the donor and presence of CVD risk factors, with almost a 20-fold increase in the 72 compared to the 6-month-old donor (
Fig. B
).To specifically target the atherosclerotic plaques and the plaque forming cells without affecting the endothelium, we used a cell-penetrating peptide (p5RHH) (
Fig. C
) that self-assembles with synthetic mRNA to form nanoparticles that exclusively target denuded regions of endothelium and atherosclerotic plaques (
Fig. D
). We will deliver small interfering RNA specific to IL-1β and a microRNA switch that consists of synthetic mRNA encoding a cell-cycle inhibitor, p27, that includes a single target site for the endothelial cell specific miR-126, which we previously showed to selectively inhibit intimal hyperplasia and infiltrating immune cells while sparing the vascular endothelium (
Fig. E
). This innovative combination of multiple RNA therapeutics into a single nanoparticle will advance the field of site- and cell-selective anti-atherosclerotic therapy.
Abstract 15522: Segmentation Improves Deep Learning Accuracy for Differentiating Non-Ischemic and Ischemic Cardiomyopathy Using Cardiac Mri Cine Imaging
Authors: Nakashima Makiya , Cockrum Joshua , Salam Donna , Mazumder Samia , Sreedhara Karthik , Kapadia Samir R , Svensson Lars G , Grimm Richard A , Nguyen Christopher , Tang Wai Hong W , Chen David , Kwon Deborah H
Published: June 2023

Background:
Deep learning (DL) models typically interpret images without prior knowledge of anatomic significance. However, pathophysiology is highly classified by human definitions according to underlying affected anatomy. Therefore, we examine the impact of introducing explicit knowledge of anatomy through cardiac contours on cardiac magnetic resonance images (CMR) to DL models. The DL models were then trained to differentiate between ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM) using late gadolinium enhanced (LGE) CMR.

Method:
We evaluated 301 CMR studies; ICM (n=176) and NICM (n=125). Manual contouring of LGE images was performed using CVI42 (Circle, Ontario). We compared a radiomic and end-to-end DL approach to identify cardiomyopathy (CM) etiology from short axis LGE images. Patients are randomly assigned to training (70%) and testing (30%). Model performance was assessed with area under curve (AUC).

Result:
Table 1 shows the results of radiomic and deep learning approaches to differentiate NICM and ICM. Segmented/manually contoured images with removal of non-cardiac structures greatly improved classification accuracy across all deep learning models. The average improvement in AUC was 0.163 when using segmented images compared to the full images. Furthermore, the deep learning models outperformed the radiomics models. The best radiomic model and deep learning model achieved AUCs of 0.914 and 0.947, respectively. Both radiomic based models achieved AUCs above 0.874 while all 2D deep learning models with segmented images achieved AUCs above 0.875. The two 3D deep learning models which utilize 3D convolutions provided lower AUCs ranging between 0.743 and 0.900.

Conclusion:
Manual segmentation of LGE images improved the ability to train DL models with fairly small volumes of labeled data, resulting in higher classification accuracy.

Table1 AUCs of various models.
Abstract 15523: Breaking Bad - Severe Mechanical Hemolytic Anemia After Failed Mitral Valve Repair
Authors: Goel Akshay , Lloji Amanda , Sharedalal Parija , Mcmaster Matthew W , Shah Neal , Harburger Joseph , Spevack Daniel , Ohira Suguru , Kai Masashi , Cooper Howard A
Published: June 2023

Introduction:
Hemolytic anemia is a rare complication of mitral valve repair surgery. Mechanisms include a high-velocity regurgitant jet striking the annuloplasty ring or displacement of the annuloplasty ring with para-annular leak.

Case Report:
A 66 year old man with a past history of coronary artery disease was found to have severe, eccentric mitral regurgitation (MR) due to anterior mitral valve leaflet prolapse/flail at the A2 segment. At another institution, he underwent surgical mitral valve repair involving chordal transfer from P2 to A2 segment, suture closure of the resulting P2 defect, and ring annuloplasty. Intra-operative transesophageal echocardiography confirmed the elimination of MR. Three weeks later the patient presented with fatigue and cola-colored urine. Physical examination revealed a murmur of MR. Lab tests were consistent with severe hemolytic anemia, including hemoglobin of 6 g/dL, indirect hyperbilirubinemia, elevated lactate dehydrogenase, and a low haptoglobin level. Peripheral blood smear showed dysmorphic red blood cells suggestive of mechanical lysis. The patient required multiple transfusions of packed red blood cells. Acute kidney injury developed and was attributed to pigment nephropathy. He was transferred to our institution.

Decision-making:
Recurrent MR from failure of recent mitral valve repair was suspected. Transthoracic and transesophageal echocardiography confirmed severe eccentric MR. The Heart Team recommended re-operation. In the operating room, the suture repair of the P2 defect was found to have dehisced. Re-repair was deemed infeasible, and the mitral valve was replaced with a porcine bioprosthesis. Post-operatively, hemolysis resolved and renal function recovered.

Conclusion:
This case illustrates the importance of suspecting hemolysis from recurrent MR in patients presenting with unexplained anemia after mitral valve surgery. Re-operation is generally required to treat this rare condition.
Abstract 15530: Renal Outer Medullary Potassium (Kir 1.1) is not the Kir Subunit of a Cardioprotective, Diazoxide - Mediated Mitochondrial Adenosine Triphosphate - Sensitive Potassium Channel
Authors: Wang Jie , Sangalang Janelle , Papanicolaou Kyriakos , Salazar Benjamin , Holmes Sari , Orourke Brian , Lawton Jennifer S
Published: June 2023

Objective:
The adenosine triphosphate-sensitive potassium (K
ATP
) channel opener diazoxide (DZX) mimics ischemic preconditioning and is cardioprotective. The molecular mechanism of action is unknown, although several mitochondrial candidate protein targets have been proposed. We suggested that cardioprotection occurs at a non-sarcolemmal channel, requires the inhibition of succinate dehydrogenase, and involves K
ATP
channel subunit SUR1. The renal outer medullary potassium channel (ROMK, or Kir1.1) subunit was proposed as the Kir subunit of a mitochondrial (m)K
ATP
channel. We tested the hypothesis that genetic deletion of ROMK will result in loss of DZX cardioprotection in a model of prolonged ischemia with cardioplegia.

Methods:
Mice lacking ROMK in cardiac myocytes (cKO) and wild-type (WT) litter mates were randomly assigned to 90 min. global ischemia in a Langendorff model following hypothermic hyperkalemic cardioplegia (CPG) or CPG + DZX (100 μM/L) (N=6-9 per group). Left ventricular developed pressure (LVDP), end diastolic pressure (EDP), and coronary flow were compared before and after global ischemia. Data acquisition and interpretation were blinded to group.

Results:
Similar to previous results, prolonged global ischemia was associated with a reduction in LVDP and an increase in EDP with CPG that was prevented by DZX in WT. Unexpectedly, ROMK (cKO) mice were equally responsive to DZX (Figure), indicating that DZX protection is not mediated by ROMK channels.

Conclusions:
Genetic deletion of ROMK in cardiac myocytes does not negate cardioprotection provided by DZX, indicating ROMK is not a subunit of a cardioprotective mK
ATP
channel. Alternate proposed DZX-sensitive target channels or mechanisms of action remain to be tested. Identification of the specific subunits of a mK
ATP
channel would allow for targeted pharmacologic therapy to reduce myocardial stunning following prolonged ischemia, similar to that seen following cardiac surgery.
Abstract 15535: A Case of Suspected Menstruation Induced QTc Prolongation Leading to Torsades De Pointes
Authors: Gardy Adam , Miller Joselyn , Konstantinidis Ippokratis , Ferreira Jennifer , Conner Chad , Saucier Stephanie
Published: June 2023

Estrogen is known to produce changes in cardiac electrophysiology specifically in premenopausal women, increasing the risk of arrhythmias. We report a case of Torsades de Pointes (TdP) in a young premenopausal female.

A 25-year-old female with a history of anxiety presented to the emergency room (ED) with several days of vomiting. While in the ED, she had an unwitnessed syncopal event, and was found to be in pulseless ventricular fibrillation (V-Fib) . She required one defibrillation to obtain return of spontaneous circulation (ROSC). Initial work up showed calcium 7.6 mg/dl, phosphorous 1.1 mg/dl, magnesium 2.4 mg/dl, potassium 4.0 mg/dl. Remainder of electrolytes were normal. Toxicology screen was positive for cannabinoids. Post ROSC EKG showed sinus tachycardia at a rate of 103bpm with a prolonged QTc of 531ms. Patient was not on any medications outpatient. On further discussion, patient reported no prior history of syncopal episodes, palpitations, and denied any family history of sudden cardiac death. She did report she was presently on her menses. Shortly after admission, she had recurrent polymorphic ventricular tachycardia which degenerated to TdP. She was loaded with magnesium. Echocardiogram showed an ejection fraction (EF) of 35-39% and global hypokinesis. Diagnostic left heart catheterization was performed revealing clean coronaries. Cardiac MRI revealed EF of 43% without any late gadolinium enhancement. Her QTc remained prolonged even with electrolyte normalization. She underwent successful ICD placement and remained event free during the remainder of the hospital course. She will undergo genetic work up for long QT syndrome.

Female sex hormones, specifically estrogen, have been described in literature as pro-arrhythmic given its effects on QT prolongation and ion gated channels. Prior cases of menstruation dependent arrhythmias have speculated that the abrupt reduction in estradiol prior to menstruation is associated with increased cyclic adenosine monophosphate dependent arrhythmogenicity. This case highlights the multifactorial etiology of sudden V-Fib arrest in a young female, and the importance of understanding the role that sex hormones play in the underlying pathogenesis.
Abstract 15603: Simultaneous Suction Debulking of a 3 Cm Lead Vegetation in the Right Ventricle During Extraction
Authors: Mazhar Naveed , Jamal Shakeel , Sheikh Ali , Qintar Mohammed , Osman Abdul-Fatawu
Published: June 2023

A 49-year-old male with a history of NICM EF 25% with dual-chamber AICD, lupus with nonbacterial endocarditis of aortic valve, IVC filter for recurrent DVT/PE presented with septic shock due to MRSA osteomyelitis and bacteremia. TTE showed 1.8 cm vegetation. The patient had idiopathic thrombocytopenic purpura, for which IVIG was administered. To avoid obligatory systemic exposure to heparin in the setting of ITP with a larger evacuation system and crossing the IVC filter with a large bore cannula, it was decided to proceed with Penumbra evacuation of lead vegetation with simultaneous laser extraction. A short 16F sheath was inserted through the right femoral vein for the procedure. A12F Medtronic Cryo Flex sheath was advanced through the IVC filter under fluoroscopy to provide steerability in the right atrium. TEE-guided Flex sheath positioned abutting the mass/vegetation. Suction only partially retrieved the mass. RA lead was removed using mechanical extraction tools via the left chest pocket. On repeat TEE evaluation, the mass/vegetation was 3 cm on the RV lead. Since we could not aspirate the mass, we used the extraction tools to peel the mass off the lead while providing simultaneous negative suction through the Penumbra cannula. The lead was successfully extracted. TEE showed no residual mass, no significant change in tricuspid regurgitation and no pericardial effusion. Mass biopsy showed calcified blood clots. The patient was discharged on IV antibiotics.

Discussion:

Most cases to date report using larger systems like AngioVac for extracting larger vegetations/masses with lead extraction. Aspiration tools have been shown to extract malleable masses with lesser procedural-related morbidity. Peeling and aspiration can be used concurrently to remove these masses without significant blood loss, downstream sheading and the need for systemic anticoagulation. Further technique development can benefit in removing under such challenging scenarios.
Abstract 15627: Inferior Vena Cava Filter Strut Fracture and Migration to the Right Ventricle in Post-COVID Patient With Intractable Cough
Authors: Kumar Sachin , Furqan Muhammad M , Miyasaka Rhonda , Shah Gautam
Published: June 2023

Background:
Inferior vena cava (IVC) filter fracture and migration of the fractured strut is a rare but potentially dangerous complication. We report a case of fractured IVC strut migrated to the right ventricle (RV) in a patient who was evaluated for persistent cough.

Clinical Case:
A 69-year-old male presented to his primary care physician for the evaluation of intractable cough and shortness of breath. Past medical history was significant for recurrent unprovoked deep vein thromboses treated with an IVC filter 15 years ago. He had COVID19 infection six months prior to current presentation. A computed tomography (CT) scan of the chest was ordered to screen for underlying pulmonary disease. CT scan showed no pulmonary process, but revealed a linear radiopaque foreign body in the RV of the heart. His cough was considered to be a sequela of his prior COIVD19 infection.

Decision-making:
To better characterize this foreign body in RV, a transesophageal echocardiogram was performed. This showed a prominent linear echo density on the tricuspid valve chord in the RV. On careful review of the CT scan of the chest and comparison with prior CT scans, it was found that one of the IVC filter strut at 9 o’ clock position was missing. The ‘foreign body’ in the RV had the same size as the remaining struts of the IVC filter. Given that the patient did not have any symptoms or complications from the incidentally found fractured strut, decision was made to not retrieve it with a percutaneous or surgical intervention.

Conclusion:
Significant variations in the intra-abdominal pressure may contribute to metal fatigue potentially leading to IVC filter strut fracture and migration to the RV. This underscores the importance of timely removal of IVC filters. Uncomplicated migrated IVC filter struts may be left unretrieved and patients can be followed clinically.
Abstract 15628: Incidence, Complications, and Outcomes of Non - ST Elevation Myocardial Infarction in Patients Presenting With Acute Ischemic Stroke
Authors: Mehta Shivani
Published: June 2023

Background:
Acute myocardial infarction may concomitantly occur with acute ischemic stroke. The incidence,complications and outcomes of acute Non- ST elevation Myocardial infarction in acute ischemic stroke are not well studied.

Methods:
We examined hospitalized patients (n = 1,726,265) with acute ischemic stroke that were included in National Inpatient Sample 2016-2019. Acute ischemic stroke and NSTEMI were defined by using International classification of disease (ICD -10). STEMI patients were excluded. Multivariable logistic regression analysis was used to examine association of NSTEMI with outcomes. A subgroup analysis of NSTEMI patients that underwent PCI (with or without angioplasty) was also performed.

Results:
Of the total stroke patients, 27630 (1.6%) patients (mean age 73.5, 52.2% females) had NSTEMI diagnosed during the hospitalization. Of these, 3890 (6.32%) died in NSTEMI group and 57670 (93.68%) died in non NSTEMI group. The commonest complications in NSTEMI group were cardiogenic shock 25% , cardiac tamponade 13.8% , and septic shock 12.1%. NSTEMI in stroke patients were associated with several complications and mortality (OR 2.73, 95% CI 2.57-2.90, p value <0.001). While, PCI was performed in 43.3% of NSTEMI patients, there was no increase in bleeding complications and there was reduced risk of mortality associated with PCI (OR 0.34, 95% CI 0.22-0.52, p<0.001)[FIGURE].

Conclusion:
NSTEMI even though not frequent in patients with stroke but was associated with increased risk of complications and mortality. PCI was associated with reduced risk of mortality and no increase in bleeding complications.
Abstract 15632: Rv Dysfunction and the Risk of Mortality in Cardiomyopathy Patients Who Suffered a Cardiac Arrest
Authors: Zacharia Effimia , Istvanic Filip , Saba Samir
Published: June 2023

Background:
Right ventricular (RV) dysfunction has been associated with higher mortality in patients who suffer a cardiac arrest. However, the role of RV dysfunction in patients with known cardiomyopathy (CM) (EF<50%) who suffer cardiac arrest from a shockable rhythm is not well examined.

Aim:
To assess the relationship between RV dysfunction and mortality in patients with cardiac arrest from a shockable rhythm without an ICD.

Methods:
We included patients with CM of any etiology who were hospitalized for the first time with cardiac arrest at a tertiary care center between 2011 and 2017. We examined in-hospital as well as long-term mortality. RV dysfunction was defined based on standard echo parameters.

Results:
A total of 208 patients were admitted to the hospital with cardiac arrest from a shockable rhythm (VT/VfIb) and 139 of those had no ICD at the time of the cardiac arrest. Out of those 139 patients, 48 had RV dysfunction. Patients with RV dysfunction had higher in-hospital mortality (44.7% vs 15.1%, p<.001). Over a mean follow-up of 2.9±3.2 years, patients with RV dysfunction had higher long-term mortality rates (72.9 vs 53.8%, p=.029) as well as shorter mean survival time (33.2, CI [20.6-45.8], vs 66.0 [53-78.9] months, p=0.005, Figure). In a Cox regression model, patients with RV dysfunction had higher long-term mortality rates when adjusting for EF, initiation of new AAD, electrolyte abnormalities and new ischemia (HR 1.68, 95% CI [1.05-2.69], p=.028). During hospitalization, patients with RV dysfunction needed advanced HF treatment options (inotropes, OHT) more frequently compared to patients without RV dysfunction (70.8 vs 46.2%, p=.005).

Conclusions:
RV dysfunction is an independent predictor of mortality in patients with cardiac arrest from a shockable rhythm who do not have an ICD. Further studies should investigate whether the presence of RV dysfunction alone should be taken into consideration for decisions on ICD implantation in patients with CM.
Abstract 15659: Development of Novel EMAP-II Neutralizing Antibody Therapy for HIV-Associated Pulmonary Hypertension via Abrogation of HIV-Nef Induced Pulmonary Endothelial Damage
Authors: Chelvanambi Sarvesh , Noda Moraima , Clauss Matthias A
Published: June 2023

Rationale:
People living with HIV experience increased rates of cardiovascular co-morbidities including pulmonary hypertension (600-fold higher prevalence) despite immediate prescription of combined antiviral therapy (ART) upon HIV diagnosis. Previously, we reported that the virally encoded HIV-Nef protein persists in extracellular vesicles (EV) isolated from bronchoalveolar lavage fluid of aviremic HIV patients on ART. Interestingly, Nef-positivity correlated with increased EMAPII levels, a cellular protein which when released extracellularly specifically amplifies endothelial apoptosis. We hypothesize that Nef-EMAPII signaling axis induces endothelial apoptosis and senescence, which could give rise to apoptosis-senescence-resistant, plexiform lesion-forming endothelial cells.

Methods and Results:
Co-culture with Nef EV producing SupT1 T-cells induces endothelial senescence quantified using senescence associated marker-p16INK4a (p<0.001) which corresponds to increased EMAPII surface expression. Nef induced endothelial senescence as quantified by β-Galactosidase activity was blocked with EMAPII neutralizing antibody (Fig). Transgenic mice with endothelium specific Nef expression had elevated EMAP II surface expression. Two-dose injection of EMAPII neutralizing antibodies (1 mg/mouse, sc) abrogates apoptosis induction as determined by cleaved caspase 3+ pulmonary endothelial cells (p<0.001). Furthermore, Nef Tg mice derived pulmonary endothelial cells had reduced colony formation (p<0.001) which is being tested with EMAPII neutralization as a therapeutic agent.

Conclusion:
Nef induced apoptosis and cellular senescence can be targeted with EMAP II neutralizing antibodies both
in vitro
and
in vivo
. These data suggest that A) Nef can give rise to apoptosis-senescence-resistant plexiform lesion forming endothelial cells and B) neutralizing EMAPII antibodies can be employed to block progression of PAH.
Abstract 15672: Cost-Effectiveness of Team-Based Care for Hypertension
Authors: Rao Aditi S , Bryant Kelsey B , Cohen Laura P , Dandan Nadine , Kronish Ian M , Barai Nikita , Fontil Valy , Zhang Yiyi , Moran Andrew E , Bellows Pharmd Brandon K
Published: June 2023

Introduction:
Team-based care (TBC), typically involving a physician and non-physician working in collaboration, is more effective than usual physician-only care in reducing blood pressure (BP). This analysis estimated the cost-effectiveness of TBC strategies vs. usual care over 10 years.

Methods:
We used the Cardiovascular Disease (CVD) Policy Model to project long-term BP, CVD events, and survival in a nationally representative cohort of 10,000 US adults (aged ≥20 years) with uncontrolled BP (≥140/90 mmHg) from the National Health and Nutrition Examination Survey. We compared (1) usual care, (2) TBC with a registered nurse providing hypertension counseling, and (3) TBC with a pharmacist providing counseling and titrating medications. BP reductions with TBC were derived from meta-analysis; other inputs were derived from published literature and publicly available data. TBC interventions were simulated to last six months, after which individuals were assumed to return to usual care. The outcomes were mean per-patient direct healthcare costs (2021 USD), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) from a US healthcare sector perspective. Sensitivity analyses assessed the impact of TBC program design and hypertension care process parameters on the cost-effectiveness of TBC.

Results:
The mean (SD) age was 59.8 (16.6) years, 50.0% were female, and mean baseline systolic BP was 150.9 (14.2) mmHg. At 10 years, TBC with nurse counseling and with pharmacist titration were projected to result in mean (95% uncertainty interval) 0.6-mmHg (0.4, 0.8) and 2.8-mmHg (2.2, 3.4) greater reductions in systolic BP. Both TBC strategies were estimated to dominate (i.e., cost less and more effective) usual care, with nurse counseling projected to cost -$617 (-$1539, $364) and with pharmacist titration -$416 (-$1400, $470) less than usual care. Compared with TBC with nurse counseling, TBC with pharmacist titration had an ICER of $13,000/QALY gained (88.0% probability ICER <$50,000/QALY gained). The ICER was most sensitive to the probability of pharmacist medication intensification.

Conclusions:
TBC with pharmacist titration is a cost-effective strategy to reduce CVD events in US adults with uncontrolled hypertension.
Abstract 15678: The Introduction of Novel Heart Failure Therapy in Patients With Non-Compaction Cardiomyopathy Leads to an Improvement of Heart Failure
Authors: Cerar Andraz , Frljak Sabina , Okrajsek Renata , Zorz Neza , Poglajen Gregor , Zemljic Gregor , Sebestjen Miran , Vrtovec Bojan
Published: June 2023

Introduction:
In patients with noncompaction cardiomyopathy (NCC) no heart failure (HF) therapy has been shown to improve the left ventricle ejection fraction (LVEF). Sudden cardiac death (SCD) or need for heart transplantation (HTx) or left ventricle assist device (LVAD) implantation have been described. The effect of novel HF therapy, such as angiotensin receptor and neprilysin inhibitor (ARNI) and sodium glucose co-transporter 2 inhibitors (SGLT2i) remains unclear.

Hypothesis:
We sought to analyze a potential recovery of cardiac function in patients with NCC after introducing the novel HF therapy.

Methods:
We have prospectively enrolled 41 (33 male, 8 female) patients with NCC, confirmed by cardiac MRI from 2018 to 2021. The average age was 49±16.3 years. At inclusion, echocardiography was performed to determine the left ventricle end-diastolic diameter and volume (EDD and EDV) and LVEF; serum levels of NT-proBNP have also been obtained. ARNI and SGLT2i have been introduced into patients’ therapy and up titrated to maximal tolerated dose. After 1 year follow up investigations, performed at patients' inclusion, have been repeated.

Results:
Of 41 patients enrolled 23 patients (56%) had echocardiographic evidence of myocardial recovery (Group A), defined by improvement of LVEF above 40% (LVEF increased from 31±6.6% to 48±5.2%. 9 patients (22%) showed no significant LVEF improvement (Group B, LVEF increased from 26±8.0% to 33±2.6%). 9 patients were excluded (2 due to SCD, 7 had HTx or LVAD implantation performed). The two groups did not differ in sex (male 41% vs. 39% in Group B, P=0.51), age (51±17.2 years vs. 46±15.2 years, P=0.72), sodium (140±2.6mEq/L vs. 138±1.8mEq/mL, P=0.22), creatinine (82±24μmol/L vs. 87±18 μmol/L, P=0.51) or bilirubin levels (17±12μmol/L vs. 21±12μmol/L, P=0.42). When compared to Group B at inclusion, Group A had significantly higher LVEF (31,6±6,6% vs. 26,5±8,0% in Group B, P=0.033) and lower NTproBNP levels (1619±1505pg/mL vs. 4902±3795pg/mL, P<0.001).

Conclusions:
In patients with NCC, the introduction of novel HF therapy seems to be connected with significant reverse remodelation of the myocardium. The improvement has been shown to be more pronounced in NCC patients with better LVEF and lower neurohormonal activation.
Abstract 15705: Immunomodulatory Titanium Carbide MXene Nanosheets for Treatment of Cardiac Allograft Vasculopathy
Authors: Yan Weiang , RAFIEERAD ALIREZA , Alagarsamy Keshav Narayan , ARORA Rakesh C , Dhingra Sanjiv
Published: June 2023

Introduction:
Cardiac allograft vasculopathy is an aggressive form of atherosclerosis and a major cause of mortality among patients with heart transplants. Blood vessel endothelial cells stimulate alloreactive T-lymphocytes to result in sustained inflammation. MXenes are an emerging class of nanomaterials that have been shown to possess immunomodulatory properties. Herein, we report the first application of titanium carbide (Ti
3
C
2
T
x
) MXene nanosheets for prevention of allograft vasculopathy.

Methods and Results:
Detailed physicochemical characterization of Ti
3
C
2
T
x
MXene nanosheets was performed using scanning/transmission electron microscopy, x-ray diffraction, and x-ray photoelectron spectroscopy. Ti
3
C
2
T
x
MXene nanosheets were 2 to 5 μm in size and enriched with biologically active surface groups.
In vitro
, MXene nanosheets interacted with human umbilical vein endothelial cells (HUVECs) and downregulated the expression of genes involved in alloantigen presentation through the class I major histocompatibility complex (IRF1, TAP1, B2M), and reduced the activation and pro-inflammatory polarization of co-cultured allogeneic lymphocytes. Consequently, RNA-Seq analysis of these lymphocytes showed that treatment with MXene nanosheets downregulated genes responsible for transplant-induced T-cell activation, cell-mediated rejection, and development of allograft vasculopathy. Furthermore, gene set enrichment analysis revealed significant negative enrichment of genes involved in interferon alpha/beta and interferon gamma signaling. Finally, in an
in vivo
rat model of allograft vasculopathy, treatment with Ti
3
C
2
T
x
MXene nanosheets reduced lymphocyte infiltration and preserved medial smooth muscle cell integrity within transplanted aortic allografts.

Conclusion:
These findings support the potential of Ti
3
C
2
T
x
MXene nanosheets for prevention and treatment of allograft vasculopathy and other inflammatory diseases. This research also opens the door to development of Ti
3
C
2
T
x
MXene technologies for other immune-sensitive regenerative medicine applications.
Abstract 15707: Age Does Not Modify the Impact of Natriuretic Peptide-Guided Therapy on Clinical Outcomes or Serial Natriuretic Peptide Levels
Authors: Hood Caleb J , Gupta Anand , Hendren Nicholas S , Farr MaryJane A , Drazner Mark H , Tang Wai Hong W , Grodin Justin L
Published: June 2023

Introduction:
Older age is independently associated with greater NT-proBNP levels. As such, the aim of this study was to establish the influence of age on serial NT-proBNP levels over time and the impact of age on response to natriuretic peptide-guided therapy (NPGT) versus usual care for heart failure with reduced ejection fraction (HFrEF).

Hypothesis:
Age will modify the effect of NPGT on serial NT-proBNP in patients with HFrEF.

Methods:
Using data from GUIDE-IT, the impact of age on the association of NPGT with serial NT-proBNP and long-term outcomes was assessed. Time-to-event analyses and generalized linear mixed modeling were used to evaluate the effect of age, by quartile, on long-term outcomes and serial NT-proBNP by randomized treatment (NPGT vs. usual care), respectively.

Results:
In this cohort (N=893), the median age was 63 [range 21-90, IQR 53-71] years and was 32% female and 36% black race. Age was modestly correlated with NT-proBNP (Spearman rho 0.34, p<0.001). At baseline, older age was associated with lower doses of ACEI/ARB (p-trend 0.019) and aldosterone antagonist use (p-trend<0.001), but not beta-blocker use (p=0.06). Older age was associated with a greater risk of all-cause death (log-rank, p<0.001) but not associated with a greater risk of combined CV death or HF hospitalization (log-rank, P=0.56). Although older age was associated with greater NT-proBNP levels over time (Q4 vs. Q1 beta 2.1 x pg/mL/days, p<0.001), it did not modify the association of NPGT on serial NT-proBNP (
Figure,
Q4, Q3, and Q2 vs. Q1 by treatment arm, p-interaction>0.09 for all). Age also did not modify the impact of NPGT on either mortality or the composite, CV death or HF hospitalization (P-interaction>0.05 for both).

Conclusions:
Older age was associated with greater NT-proBNP levels. However, age did not modify the association of NPGT on clinical outcomes or serial NT-proBNP. These data do not support the hypothesis that age modifies the NT-proBNP response to HFrEF treatments.
Abstract 15727: Cancer and Atherosclerosis Share Numerous Pathogenic Drivers Representing Novel Translational Targets for Mutual Benefit
Authors: Baylis Richard , Gao Hua , Wang Fudi , Bell Caitlin , Luo Lingfeng , Erdmann Jeanette , Bjorkegren Johan , Klarin Derek , Leeper Nick J
Published: June 2023

Cancer and cardiovascular disease make up nearly half of all deaths in the United States. Despite knowing a great deal about each of these diseases individually, surprisingly little is known about how these diseases interact within patients or the common dysregulated genes and pathways that these diseases share. These diseases are known to share numerous risk factors and emerging epidemiologic data suggests that the presence of coronary artery disease (CAD) increases the risk of developing cancer. In addition, studies like the CANTOS trial have shown that targeting mutually detrimental pathways could yield benefit for both diseases. To understand the relationship of cancer and CAD, we tested two hypotheses, 1) the similarities between cancer and CAD are explained, in part, by shared genetic factors and 2) these diseases share dysregulated processes/pathogenic drivers and that targeting these processes could result in mutual clinical benefit. To test these hypotheses, we assessed the genetic correlation of CAD and each cancer subtype in the UK biobank. This identified a surprising genetic overlap between prostate cancer and CAD. However, the other cancers lacked significant genetic correlation with CAD, suggesting that common genetic factors were unlikely to be mediating their interaction. To identify common pathogenic drivers, we used transcriptomic data that had been correlated with either cancer survival or CAD disease severity/outcomes to generate transcriptional risk profiles for each disease. We then intersected these data to identify mutually detrimental processes, which included several known pathways including inflammation and hypoxia but also numerous novel pathways. Interestingly, we found that many cancers were indistinguishable from CAD based on their transcriptomic risk profile. Next, we used the drug prediction algorithm, OCTAD, to identify novel drug targets for each disease state and then validated our predictions using a pharmacovigilance approach with EMR data. Taken together, our study suggests that the interaction of cancer and CAD is primarily driven by shared pathogenic drivers rather than shared genetic predisposition and that targeting these processes may allow for mutual clinical benefit.
Abstract 15728: Apixaban Use in Patients Supported by Durable Left Ventricular Assist Device
Authors: Slaughter Mark S , Pahwa Siddharth , Moore Stephanie , Samson Rohan , Costelle Devan , Trivedi Jaimin
Published: June 2023

Introduction:
Coumadin is currently the standard of care for long-term anticoagulation in patients supported with a left ventricular assist device (LVAD). Coumadin requires frequent testing and is associated with adverse events. The aim of this study was to evaluate the routine use of Apixaban in contemporary LVAD patients.

Methods:
A single center LVAD database was retrospectively queried to identify HeartMate 3 (HM3) patients between January 2016 and May 2022. Patients were divided into 2 groups based on anticoagulation received: Coumadin vs Apixaban. The primary outcome was 1-year mortality and secondary events of freedom from bleeding and stroke at 1 year. Univariate statistics and Kaplan-Meier curves were used for data analysis.

Results:
A total of 67 consecutive patients underwent HM3 implant during the study period: 20 (30%) coumadin and 47 (70%) apixaban. There was no difference in gender, age, BMI, creatinine, previous stroke or INTERMACS level between groups (Tabe1). Total days of support: Coumadin 25,750 days and Apixaban 16,556 days. The mortality at one year was comparable (5% v. 6%, p=0.12). The coumadin group had higher overall bleeding events (55% v. 17%, p<.01) and freedom bleeding at 1 year was better in apixaban group (86% v. 64%, p=0.04). Freedom from stroke at 1 year was comparable between the groups (95% v. 97%, p=026). Survival at 1 year with no stroke or bleeding was similar (Figure 1).

Conclusion:
In this single center retrospective analysis, Apixaban in patients with a durable LVAD has shown reduced bleeding events and comparable stroke and survival outcomes. This early experience demonstrates that Apixaban is a possible alternative to Coumadin.
Abstract 15731:
Rpl13a
Small Nucleolar RNAs Promote Atherosclerosis and Oxidative Stress
Authors: Zhang Lisheng , Wu Jiao-Hui , Elliott Brittany A , yin xinhe , Snow Kamie P , FREEDMAN Neil J , Holley Christopher L
Published: June 2023

Reactive oxygen species (ROS) exacerbate atherosclerosis (athero). ROS levels are elevated by specific non-coding, small nucleolar (sno) RNAs encoded within introns of the
Rpl13a
gene. We therefore tested the hypothesis that these snoRNAs promote athero, using “snoKO” mice deficient in
Rpl13a
snoRNAs, but not in
Rpl13a
itself. ROS levels assessed by CellROX Orange were 35% lower in snoKO than snoRNA
+/+
aorta frozen sections (
p
<0.01). After 14 wk on Western diet, female snoKO/
Apoe
-/-
unexpectedly showed total cholesterol levels 20% higher than
Apoe
-/-
mice in (1,046 vs 869 mg/dl,
p
<0.05). Despite this, neointimal lesions in brachiocephalic artery (BCA) cross-sections were 50% smaller in snoKO/
Apoe
-/-
than in
Apoe
-/-
mice, and lumen size was 45% larger (both
p
<0.01, n=8/group). Similar data were obtained in males: snoKO/
Apoe
-/-
mice had 40% smaller BCA lesion areas (
p
<0.02, n=8/group). After being stained for cholesteryl ester with BODIPY, for ACTA2 by immunofluorescence and for DNA (Hoechst), BCAs from female snoKO/
Apoe
-/-
mice (n=9) demonstrated 50% less foam cell-positive and 95% more ACTA2
+
area, 40% less necrotic core area, and a 60% lower prevalence of ACTA2
+
foam cells (
p
<0.05 for each). Thus,
Rpl13a
snoRNAs promote vascular ROS and athero. Assessed by MitoSOX Red, ROS levels were 25% lower in snoKO than WT M1-polarized bone marrow-derived Mϕs in vitro (n=3, p<0.05). To identify mechanisms linking the
Rpl13a
snoRNAs to ROS and athero, we performed LC-MS/MS on WT and snoKO aortic SMCs. COX4I2 was expressed 5.7-fold higher in snoKO than WT SMCs by MS/MS, and 2.5-fold higher in snoKO SMCs by immunoblot (n=3/group,
p
<0.05). As part of mitochondrial complex IV, COX4I2 lowers cellular ROS levels. We used CRISPR/Cas9 to create 293T cells lacking either the
RPL13a
-snoRNA
U34A
or the irrelevant snoRNA
U25
. With mRNA from these cells we performed reverse transcription at low [dNTP] followed by qPCR (RTL-P) for
COX4I2
. Inversely proportional to the degree of mRNA 2’-
O
-methylation (mediated by snoRNAs), the RTL-P efficiency was 4-fold higher in
U34A
-knockout than control cells (3 clones/genotype,
p
<0.01). Thus,
COX4I2
mRNA appears to be regulated by
RPL13A
-snoRNA-guided 2’-
O
-methylation in a manner that could link
Rpl13a
snoRNAs, vascular ROS, and athero.
Abstract 15749: Outcomes of Fluoroless vs. Fluoroscopy-Guided Left Atrial Appendage Electrical Isolation During Catheter Ablation of Atrial Fibrillation
Authors: Romero Jorge , Gabr Mohamed , Alviz Isabella , Rodriguez Daniel , Purkayastha Sutopa , Cerna Luis , Matias Jose , Velasco Alejandro , Natale Andrea , Diaz Juan C , Marin Jorge , Della Rocca Domenico G , Di Biase Luigi
Published: June 2023

Introduction:
Fluoroscopy-guided catheter ablation remains a common practice. With the presence of technologies such as intracardiac echocardiography (ICE) and electroanatomic mapping (EAM), it is possible to perform fluoro- and lead-free procedures to avoid the hazards of prolonged radiation exposure. Left atrial appendage electrical isolation (LAAEI) is a proven e!ective ablation strategy for atrial fibrillation (AF). We sought to assess the characteristics, complications, and outcomes of fluoroscopy-guided LAAEI and compare them to fluoroless LAAEI.

Methods:
We retrospectively analyzed patients with AF who underwent LAAEI as part of their ablation procedure. The study group included patients who underwent LAAEI either under fluoroscopy guidance or with ICE and EAM alone. We analyzed outcomes and procedural data, including procedural times, fluoroscopy times, radiation exposure (mGy), and radiofrequency times.

Results:
Overall, we analyzed 168 patients who underwent LAAEI; 110 under fluoroscopy guidance and 58 fluoroless. The mean procedural time was similar in both groups (248 ± 101 vs 264 ± 83 minutes, respectively, p=0.27). The mean RF time was longer in the fluoroscopy-guided group (50 ± 28.2 compared to 43 ± 17.1 minutes, respectively, p<0.001).The mean fluoroscopy time in the fluoroscopy-guided group was 25.3 ± 24.7 minutes, with mean radiation exposure of 177 ± 389 mGy. There was no difference in procedure-related complication rates ( 7 [6.3%] vs 4 [6.9%], respectively, p=0.89). At follow-up, there was no significant difference in arrhythmia recurrence rates (40.9% vs 31%, p=0.21).

Conclusion:
Fluoroless LAAEI is a safe and e!ective alternative to fluoroscopy-guided ablation, with the added benefit of averting the risks of ionizing radiation exposure.

1