bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17007: Unveiling the Immunological and Endocrine Transformations of Veins in Chronic Kidney Disease Through MYCN-AP1 Signaling Amplification
Authors: Saaoud Fatma , Martinez Laisel , Lu Yifan , Xu Keman , Shao Ying , Zhuo Jia L , Gillespie Avrum , Wang Hong , Tabbara Marwan , Salama Alghidak , Yang Xiaofeng , Vazquez-Padron Roberto I
Published: December 2023

Introduction:
The predominant selection of hemodialysis as the optimal treatment approach for patients with end-stage renal disease (ESRD) and advanced chronic kidney disease (CKD). Thus, upper extremity veins provide a functioning arteriovenous access to reduce dependence on central venous catheters. However, it is unknown whether CKD reprograms the transcriptome of veins and primes them for arteriovenous fistula (AVF) failure.

Hypothesis:
we hypothesized that CKD reprograms and transdifferentiates veins into a specialized immune endocrine organ thereby accelerating vascular inflammation.

Methods:
we performed transcriptomic analyses of bulk RNA sequencing data of veins isolated from 48 CKD patients and 20 non-CKD controls.

Results:
Our data showed that: 1) CKD induces vein conversion into immune organs through upregulation of 13 cytokine and chemokine genes, along with over 50 canonical and non-canonical secretome gene; 2) Enhancement of innate immune responses in CKD through upregulation of 12 innate immune response genes and 18 cell membrane protein genes, promoting intercellular communication including CX3CR1 chemokine signaling; 3) CKD induces upregulation of 5 endoplasmic reticulum protein-coding genes and 3 mitochondrial genes, resulting in impaired mitochondrial bioenergetics and immunometabolic reprogramming; 4) Altered fibrogenic processes in veins during CKD through upregulation of 20 fibroblast genes and 6 fibrogenic factors, leading to increased susceptibility to AVF failure; 5) Reprogramming of cell death and survival programs in CKD; 6) Reprogramming of protein kinase signal transduction pathways and upregulation of SRPK3 and CHKB in CKD; and 7) Transcriptomic reprogramming of veins and upregulation of MYCN, AP1, and Additional 11 transcription factors in CKD: implications for embryonic organ development, positive regulation of developmental growth, and vein muscle structure development.

Conclusion:
The findings unveil veins as immune-endocrine organs and illuminate the impact of CKD in upregulation of secretomes, immune cell differentiation, and vascular cell dynamics.
Abstract 17014: Differences in the Outcomes of Catheter Ablation for Ventricular Tachycardia in Patients With Ischemic versus Non-Ischemic Cardiomyopathy
Authors: Woelber Tiffany , Dhawan Rahul , Dai Qiying , Desimone Christopher V , Killu Ammar M , Siontis Konstantinos , Deshmukh Abhishek , Kowlgi Gurukripa N
Published: December 2023

Background:
Catheter ablation is an effective tool to reduce ventricular tachycardia (VT) burden. There is a lack of robust data studying the characteristics and outcomes of VT ablation in patients with ischemic (ICM) versus non-ischemic cardiomyopathy (NICM).

Aims:
The aim of this study was to assess the impact of ICM vs NICM on outcomes of VT ablation.

Methods:
A single-center, retrospective study of patients undergoing catheter ablation for VT was conducted.

Results:
A total of 168 patients, undergoing 200 VT ablation procedures, were included in this study. NICM group (112 procedures) was compared to ICM group (88 procedures). Patients in the ICM group were older (66.6 ± 13.4 vs 58.9 ± 14.4 years) and had higher rates of prior myocardial infarction (65.9% vs 3.6) and coronary artery bypass graft surgery (40.9% vs 1.8%). Overall, ICM group had more comorbidities like hypertension (80.7% vs 52.7%), diabetes mellitus (23.9% vs 12.5%), chronic kidney disease (45.5% vs 35.7%), stroke (17% vs 7.1%), and lower left ventricular ejection fraction (36.8 ± 13.2% vs 43.1 ± 14.7%). The ICM group had lower incidence of prior cardiac valvular surgery (9.1% vs 29.5%). The inducibility of VT (93% vs 93.5%; p= 1.0) and the number of different VT morphologies induced during the case (1.9 ± 1.5 vs 2.3 ± 2.5; p=0.19) was similar between the two groups. There was no acute mortality in either group. There was a non-significant trend towards greater VT recurrence in the NICM group (43.2% vs 33.3%, p= 0.19). However, patients with NICM had a lower VT-free survival as determined by Kaplan-Meier analysis (p=0.05) [Figure]. Long term mortality was higher in ICM group when compared to NICM group (18.2% vs 8.9%, p<0.01).

Conclusion:
Patients undergoing VT ablation in the NICM group when compared to the ICM group were noted to be younger, had fewer comorbidities, and lower long-term mortality. However, they had significantly less VT-free survival, likely owing to more challenging substrate responsible for VT.
Abstract 17052: Are Sex-Specific Thresholds Needed for Donor-Derived Cell-Free DNA in Rejection Surveillance? An Analysis From the Genomic Research Alliance for Transplantation
Authors: DeFilippis Ersilia M , Sweigart Benjamin A , Khush Kiran K , Shah Palak , Agbor-Enoh Sean , Valantine Hannah , Vest Amanda R
Published: December 2023

Introduction:
Non-invasive methods for surveillance of rejection are increasingly used among heart transplant (HT) recipients, including donor-derived cell-free DNA (dd-cfDNA). The purpose of the current study was to examine patterns of dd-cfDNA seen in quiescence and acute rejection in males and females.

Hypothesis:
As other cardiac biomarkers differ by sex, we hypothesized that there may be sex-specific differences in performance for detection of acute rejection.

Methods:
Patients previously enrolled in GRAfT who were ≥18 years at the time of HT were included. Rejection was defined by endomyocardial biopsy with ISHLT acute cellular rejection (ACR) grade ≥2R and/or antibody-mediated rejection ≥ pAMR 1. Median dd-cfDNA levels were compared between sexes during quiescence and rejection. The performance of dd-cfDNA by sex at or after Day 28 was assessed using AUROC. Allograft injury was defined as dd-cfDNA ≥0.25%.

Results:
After exclusions, 148 patients were included with 1109 dd-cfDNA measurements. Baseline characteristics including demographics and comorbidities were not significantly different between sexes. During quiescence, there were no significant sex differences in median dd-cfDNA (0.038% [IQR 0.001-0.167] in females vs 0.029% [IQR 0.001-0.125] in males, p = 0.21). There were no significant sex differences in median dd-cfDNA for ACR (0.33% [0.210-0.356] in females vs 0.32% [0.210-1.103] in males, p = 0.57). Overall, median dd-cfDNA levels were higher in AMR than ACR but did not significantly differ by sex (0.50% [IQR 0.180-0.820] in females vs 0.63% [IQR 0.316-1.945] in males, p = 0.51). Elevated dd-cfDNA detected ACR/AMR with an AUROC of 0.83 in females and 0.89 in males (Figure).

Conclusions:
There were no significant sex differences between dd-cfDNA levels during quiescence and rejection. Performance characteristics were similar, suggesting that similar thresholds can be used in men and women for rejection surveillance.
Abstract 17076: The Relationship Between Impaired Microvascular Function, Cardiovascular Risk Profile and Subclinical Atherosclerotic Burden in a Swedish Middle-Aged Cohort
Authors: Bergstrand Sara , Jonasson Hanna , Fredriksson Ingemar , Larsson Marcus , Ostgren Carl - , Stromberg Tomas
Published: December 2023

Introduction:
Microvascular function is associated with cardiovascular risk factors and deteriorates in individuals with cardiovascular disease.

Hypothesis:
The aim of this study was to investigate the relationship between microvascular function, cardiovascular risk profile and subclinical atherosclerotic burden.

Methods:
The study enrolled 3809 randomly selected individuals, 50-65 years old, participating in the population-based observational cross-sectional Swedish CArdioPulmonary bioImage Study (SCAPIS). Microvascular function was measured in forearm skin using an arterial occlusion and release protocol determining the peak blood oxygen saturation, OxyP. Cardiovascular risk was calculated using the updated Systematic Coronary Risk Evaluation (SCORE2; 10-year risk of fatal and non-fatal CVD events). OxyP was compared with Coronary artery calcification score (CACS) and plaques in the carotid arteries.

Results:
Individuals with OxyP values in the lowest quartile (Q1; impaired microvascular function), had a mean SCORE2 of 5.8% compared to 3.8% in those with the highest values of OxyP (Q4), a relative risk increase of 53%. In the low-risk SCORE2 level (<5% risk), 19.0% of the individuals have impaired microvascular function as compared to 48.1% in the high-risk SCORE2 level (>10% risk). OxyP was lower in individuals with coronary artery calcification (CACS>0) and those with both carotid plaque and CACS>0, as compared to individuals without subclinical atherosclerotic burden (CACS=0 and no carotid plaque; 87.5 ±5.6 % and 86.9 ±6.0 % vs 88.6 ± 5.8 %, p < 0.01).

Conclusion:
In a population without cardiovascular disease or diabetes mellitus, impaired microvascular function is associated with higher SCORE2 risk and CACS>0. Hence, assessment of microvascular function may be a useful tool for accurate cardiovascular risk prediction, in addition to imaging assessment of atherosclerosis in the coronary and carotid arteries.
Abstract 17110: Racial Differences in the Performance of the Transthyretin Amyloid Cardiomyopathy Risk Score
Authors: Chedid El Helou Michel , Gupta Mohak , Hussain Muzna , Hanna Mazen A , Jaber Wael A , Tang Wai Hong W , Collier Patrick H , Martyn Trejeeve M
Published: December 2023

Introduction:
Early diagnosis of transthyretin cardiac amyloidosis is crucial, particularly with the availability of disease-modifying therapies. Tc-99m pyrophosphate scintigraphy (PYP scan) is widely used for diagnosis. A previously validated score derived from a nearly all Caucasian cohort has shown promise in predicting PYP scan positivity in patients with HFpEF; but further assessment in a racially diverse cohort is needed.

Aims:
To evaluate the performance of the ATTR-CM score in predicting PYP scan positivity overall, and across racial groups.

Methods:
We included all patients referred for PYP with SPECT/CT at the Cleveland Clinic between 1/2012 and 1/2020 who had undergone echocardiography within one year of PYP scan. The ATTR-CM score was calculated, consisting of the following variables: Age (if 60-69, +2; if 70-79, +3; if ≥80, +4), Sex (if Male, +2), Hypertension diagnosis (if present, -1), Ejection Fraction (if <60%, +1), Posterior Wall Thickness (if ≥12 mm, +1) and Relative Wall Thickness (if >0.57, +2). A score ≥6 was considered high-risk.

Results:
The cohort consisted of 540 patients (64% white; 33% black). The overall prevalence of ATTR-CM was 28.5%, with no significant difference between racial groups (27.5% vs 29.9%; p = 0.52). A higher proportion of black patients had an EF < 40% (23.3% vs 35.4%, p = 0.01). The score showed good discrimination with an AUC of 0.816, with similar performance between racial groups (0.824 vs. 0.824; p < 0.001; Figure 2). For a score ≥6, sensitivity was 77.3% (82.7% white; 67.3% black), specificity was 70.2% (64.3% white; 80.6% black), PPV was 50.9%, and NPV was 88.6%. Similar findings were observed when considering only patients with EF ≥ 40%.

Conclusions:
The overall performance of the ATTR-CM risk score by AUC was consistently good across races. However, it was less sensitive for detecting disease in black patients. Efforts to scale ATTR-CM diagnosis tools should be mindful of racial differences in risk prediction models.
Abstract 17111: Spontaneous Regression of Cardiac Angiosarcoma in a 17-Year-Old Male
Authors: Sharrack Noor , Parent Martine , Lethaby Christopher , Farooq Maryum , Plein Sven , Kidambi Ananth
Published: December 2023

Description of Case:
A fit and healthy 17-year-old male was admitted with a 10-day history of chest pain and SOB. He was taking no medication and had no significant past medical or family history. Clinical examination revealed signs of pericarditis with widespread ST elevation and PR depression on ECG. TTE showed a moderate, global pericardial effusion. He was treated for pericarditis with anti-inflammatory medication and discharged with follow up a few weeks later. Repeat TTE demonstrated a mass in the pericardial space adjacent to the RV free wall. Urgent CMR was requested to exclude malignancy and showed a large, irregular heterogenous mass adjacent to the RA and RV with invasion into the RV free wall. CMR characterisation including first pass perfusion was indeterminate. CT TAP showed no distant metastases. Percutaneous biopsy was non diagnostic and serial CMR 3 weeks later showed significant reduction of the mass. PET-CT confirmed reduction in the size of the mass although there was moderate heterogeneous FDG uptake, more suggestive of malignancy rather than a benign lesion. Given the apparent resorption of the mass, repeat CMR was planned 3 months later. Repeat CMR (6 months after initial CMR) showed significant increase in the size of the cardiac mass. Surgical biopsy confirmed cardiac angiosarcoma and was unresectable. After MDT discussion, the patient was started on doxorubicin, dexrazoxane and pazopanib. This has failed to control the tumour, and he has now commenced a trial of paclitaxel.

Discussion:
Spontaneous regression of cardiac rhabdomyoma in infants has been described, but this does not extend to other primary cardiac tumours or adults. The re-emergence and significant increase in size of the mass suggests initial regression may have been a percutaneous biopsy effect causing collapse or resorption of the necrotic core. Suggested mechanisms include disruption of the tumour feeding artery during biopsy or activation of the immune system.
Abstract 17126: Role of Aldehydes, Transient Receptor Potential Ankyrin 1, and Catecholamines in Electronic Cigarette-Induced Endothelial Dysfunction in Mice
Authors: Jin Lexiao , Riggs Daniel , Richardson Andre , Lynch Jordan , Fryar Laura , Theis Whitney , Shirk Gregg , Miller Alexis , Lorkiewicz Pawel , Srivastava Sanjay , Bhatnagar Aruni , Conklin Daniel J
Published: December 2023

Although Electronic Nicotine Delivery Systems (ENDS)-derived aerosols induce endothelial dysfunction (ED), the mechanisms and constituents responsible for ED are unknown. Because ENDS use propylene glycol and vegetable glycerin (PG:VG) that thermally decompose into aldehydes, we hypothesized that acrolein and formaldehyde stimulate ED via the sensory transient receptor potential ankyrin-1 (TRPA1) receptor and the autonomic nervous system (ANS). To test this, female wild-type (WT) and TRPA1-null mice were exposed to either filtered air, PG:VG-derived aerosol, acrolein (AC; 1 ppm), or formaldehyde (FA, 5 ppm). Biomarkers of exposure (AC: 3HPMA; FA: 4TCA) and of harm (aortic ED; urinary catecholamines) were measured. The PG:VG and AC exposures significantly increased urinary 3HPMA levels; and the PG:VG and FA exposures significantly increased urinary 4TCA levels vs air controls. Both PG:VG and FA exposures (6h/d x 4d) in WT mice led to aortic ED (-64.6±3.8; –66.7±5.5 % ACh, respectively) vs air control (-81.5±1.5 % ACh); yet AC exposure did not induce ED (-76±2.9 % ACh). Exposures in TRPA1-null mice to PG:VG, AC, or FA did not lead to ED (-93.0±3.6; –82.8±3.1; -86.6±2.8 % ACh; respectively). As an index of ANS activation and a potential mediator of ED, urinary catecholamines (dopamine, DA; norepinephrine, NE; epinephrine, EPI; serotonin, 5HT) and metabolites were measured by UPLC-MS/MS in early (0-3h) and late (3-18h) post-exposure (PE) samples. In WT mice, PG:VG significantly increased early PE urine levels of NE (and two NE metabolites; +1.5-2.5x), DA metabolite (+1.5x), but not EPI nor 5HT; FA exposure increased DA (+3x), EPI (+2.5x), NE and NE metabolites (+1.2-2.5x), 5HT and 5HT metabolite (+2.5x) only in late PE; while AC exposure decreased early PE DA (-73%) and 5HT (-42%) levels. In TRPA1-null mice, PG:VG and AC exposures increased early PE levels of NE (+2x) and depressed EPI and 5HT levels (-40%); whereas FA exposure increased NE (+2x), EPI (+4x), and 5HT (+1.5) levels in late PE. Aldehydes induce ED through time-dependent mechanisms mediated in part by TRPA1 activation and ANS stimulation. These data indicate that ENDS use may increase cardiovascular disease risk via aldehydes generated by PG:VG independent of nicotine and flavorants.
Abstract 17145: Impact of Preoperative Levosimendan in Patients With Severe Heart Failure Undergoing Left Ventricular Assist Device Support: A Meta-Analysis
Authors: Luciano Pedro , Felix Nicole , Melo Soares Pinho de Carvalho Lara , Nogueira Alleh , Siqueira Clara , Cardoso Rhanderson , Generoso Giuliano
Published: December 2023

Introduction:
Left ventricular assist devices (LVADs) are frequently employed as a bridge to transplant or destination therapy. The implementation of preventive preoperative measures can have a beneficial impact on the prognosis of patients undergoing LVAD implantation. However, the role of levosimendan in this context remains uncertain.

Goals:
To evaluate the efficacy of preoperative levosimendan in reducing complications after LVAD implantation.

Methods:
We systematically searched PubMed, Scopus, and Cochrane Library for studies comparing the use of levosimendan before LVAD implantation vs. standard of care alone in May 2023. Statistical analyses were performed using Review Manager 5.4.1. Heterogeneity was assessed with I2 statistics.

Results:
Four studies comprising 4032 patients who underwent LVAD implantation were included, of whom 15,2% were on preoperative levosimendan. There was no significant difference between groups in 30-day mortality (OR, 0.95 [95% CI, 0.70-1.28], I2=0%, p=0.73 - Fig. 1A), right ventricular failure (OR, 0.92 [95% CI, 0.47-1.80], I2=69%, p=0.81 - Fig. 1B), or length of intensive care unit (ICU) stay (mean difference, 2.63 [95% CI, -2.07-7.33], I2=92%, p=0.27 - Fig. 1C).

Conclusions:
In this meta-analysis, the preoperative use of levosimendan was not associated with reduced mortality, right ventricular failure, or length of ICU stay in patients undergoing LVAD implantation.
Abstract 17159: Chronic Corticosteroid Immunosuppression in African American Pediatric Heart Transplant Recipients Does Not Improve Outcomes
Authors: Shwaish Natalie S , Frandsen Erik L , Kirklin James , Cantor Ryan S , Zhao Hong , Simmonds Jacob , Knecht Kenneth R , Wilkens Sarah , Shea Erin V , Zuckerman Warren A
Published: December 2023

Introduction:
Previous studies consistently demonstrate worse outcomes for African American (AA) pediatric heart transplant (HT) recipients when compared to non-AA counterparts. Medical and social factors have been implicated in this discrepancy. As such, chronic corticosteroid use as maintenance immunosuppression for AA HT patients may be beneficial, though this has not been studied.

Hypothesis:
Chronic maintenance corticosteroid therapy does not decrease rejection or graft failure in AA pediatric HT recipients.

Methods:
We performed a retrospective analysis of the Pediatric Heart Transplant Society (PHTS) database for all HT recipients <18 y.o. from January 1
st
, 2007 to June 30
th
, 2021. Retransplants and multiorgan transplants were excluded. Chronic steroid use was defined as taking oral steroids at one-year post-HT in the absence of rejection past 60 days post-HT to exclude patients who were on steroids for-cause. We used Kaplan-Meier and log-rank analyses for outcome comparisons among cohorts after the first year post-HT.

Results:
A total of 4099 patients were included, of which 780 (19%) were AA. Of the cohort, 756 (18.4%) were on chronic steroids. Within that group, 157 (20.1%) were AA. Patients on chronic steroids at individual centers ranged 0%-64.7% (median 11.5%, SD 16.9%), with no collective difference between steroid use in AA and non-AA patients. Freedom from rejection was worse in AA compared to non-AA patients, both in steroid and no steroid groups (p<0.01). In the non-AA cohort, freedom from rejection was better in the no steroid group (p<0.01). In the AA cohort, there was no statistical difference in rejection between the steroid and no steroid groups (p=0.20). Analyses of graft survival resulted in the same pattern.

Conclusion:
Use of Chronic steroids varies widely across pediatric HT centers, with no difference between AA and non-AA patients. AA patients have worse rejection and graft failure, and chronic steroid use did not affect these outcomes.
Abstract 17167: Uncontrolled Hypertension Increases Endothelin-1-Induced Contractile Response of Coronary Microvasculature Both Before and After Cardioplegia and Cardiopulmonary Bypass
Authors: Banerjee Debolina , Sabe Sharif A , Machan Jason , Sodha Neel , Ehsan Afshin , Feng Jun , Sellke Frank W
Published: December 2023

Introduction:
Hypertensive patients undergoing cardiopulmonary bypass (CPB) have worse clinical outcomes, and coronary microvascular dysfunction may play a role. Endothelin-1 (ET-1), a vasoactive biopeptide, is increased in cardiomyocytes during the hypertrophic response to hypertension and in patients following CPB. Differential effects of hypertension on coronary microvascular reactivity and molecular signaling pathways following CPB have yet to be elucidated.

Aims:
This study investigated the effects of well-controlled and uncontrolled hypertension on CPB-induced changes in coronary microvascular vasoconstriction to ET-1 and associated signaling using unique
in vitro
microvascular reactivity studies, RNA deep sequencing, and established molecular methods.

Methods:
Coronary microvessels (<200um) were harvested from atrial samples from patients with no hypertension (NH), well-controlled hypertension (CH), and uncontrolled hypertension (UH) before and after CPB.
In vitro
contractile response to ET-1 was assessed using video microscopy. Protein expression and receptor localization were measured using immunoblotting and immunohistochemistry, respectively. Enzyme-linked immunosorbent assay was used to quantify plasma concentration of ET-1.

Results:
Pre-CPB contractile response of coronary microvessels to ET-1 in UH was increased compared to NH or CH (p <0.05). Post-CPB contractile response was impaired overall (p <0.05). Between groups, contractile response in CH and NH was comparable while response in UH was higher (p <0.05). Plasma ET-1 increased post-CPB (p = 0.18). Total protein levels and localization of ET
A
R and ET
B
R were unchanged post-CPB.

Conclusions:
While CPB overall blunted vasomotor contractile response of coronary microvessels to ET-1, UH was associated with relatively increased vasoconstriction compared to CH and NH. Changes in plasma ET-1, ET
A
R and ET
B
R levels or localization did not contribute to these effects.
Abstract 17189: Association Between an Artificial Intelligence-Enabled ECG Algorithm for Detection of Atrial Fibrillation While in Sinus Rhythm, and Hospitalization for Recurrent Ischemic Stroke in the Community
Authors: Sheffeh Mohammad Ali , Medina-Inojosa Jose R , Brown Robert D , Klaas James P , Koriesh Ahmed , Medina-Inojosa Betsy , Mangold Kathryn , Estrada Magana Andres , Rabinstein Alejandro A , Noseworthy Peter A , Friedman Paul , Attia Zachi , Lopez-Jimenez Francisco
Published: December 2023

Introduction:
Artificial Intelligence-enabled electrocardiogram (AI-ECG) can estimate the probability of having atrial fibrillation (AFib) while in sinus rhythm. Recurrent stroke in subjects without known AFib may be due to undiagnosed AFib. We evaluated the association between AI-ECG AFib and recurrent ischemic stroke and with incident AFib

Methods:
Consecutive adults admitted to a Mayo Clinic or Mayo Clinic Health System hospital or to Olmsted Community Hospital for ischemic stroke between January,1,2000 and June,30,2022 were identified using the Rochester Epidemiology Project. Recurrent ischemic strokes were identified after reviewing medical records and imaging studies. We excluded those with known AFib or without ECGs within 3 years prior to the first ischemic stroke. The AI-ECG network was previously developed using 649,931 ECGs from > 180,000 subjects. The primary endpoint was recurrent ischemic stroke; secondary endpoint was incident AFib. Cox model adjusted for age, sex, and CHA2DS2-VASc2 score variables.

Results:
We included 4,816 subjects, mean age 70±15 yr, 54% male, 92% white, median CHA2DS2-VASc2 score 4 [3-5], median follow-up 3 [1-7] yr. 280 subjects (6%) had a second stroke and 366 (8%) were diagnosed with incident AFib over follow-up. Those with a positive AI-ECG AFib had an increased risk for recurrent ischemic stroke(HR 1.54, 95% CI 1.21-1.96, P<0.001 Figure A) This association remained significant after adjustment for CHA2DS2-VASc2 score(HR 1.37 95% CI 1.07-1.76, P=0.01). These associations were not affected by anticoagulation use over follow-up. AI-ECG AFib was also associated with incident AFib(HR 2.42 95% CI 1.96-2.98, P<0.001 Figure B)

Conclusions:
AI-ECG AFib predicts recurrent ischemic stroke in the community, possibly reflecting undiagnosed AFib that can be detected by AI-ECG, as it also predicts incident AFib. These results underscore the potential utility of AI-ECG for risk stratification of patients with ischemic stroke.
Abstract 17202: Cross-Species Evaluation of Cellular TNF Receptor-Associated Factor (TRAF) Expression, Regulation and Function in Murine and Human Atherosclerosis
Authors: Gissler Mark Colin , Horstmann Hauke , Westermann Dirk , Wolf Dennis
Published: December 2023

Background:
TNF receptor-associated factors (TRAFs) potently modulate immune cell function and activity in a variety of inflammatory diseases. However, due to the limited availability of viable animal models, the roles of TRAF3, TRAF4 and TRAF7 in atherosclerosis remain unknown to date. Here, we present a stepwise multiparametric approach to delineate cellular expression, regulation and implications on cardiovascular outcomes of TRAFs in murine and human atherosclerosis.

Methods:
To induce atherosclerotic lesion formation, LDLR-/- mice were fed a high cholesterol diet for 20 weeks and expression of TRAF1-7 was determined in whole tissue lysates of the murine aorta as well as on sorted leukocytes. We then performed scRNAseq and bioinformatical integration of leukocytes from human and mouse atherosclerotic plaques to analyze and compare single cell TRAF expression in both species. Finally, potential significance of cellular TRAF3, 4 and 7 expression in human atherosclerosis was assessed in three independent clinical study cohorts.

Results:
Aortic TRAF3 and TRAF4 expression was 2-fold higher in atherosclerotic mice compared to controls, whereas TRAF7 expression was significantly lower. Between species, humans exhibited higher cellular TRAF3 expression than mice. Further, TRAF7 blood expression was lower in patients with an unstable CAD angiogram than in patients with stable CAD while expression of TRAF3 in human atherosclerotic plaques was significantly higher in unstable compared to stable lesions. Finally, TRAF3 expression on circulating CD16+ monocytes determined by scRNAseq of PBMCs was substantially higher in atherosclerotic patients that died from a cardiovascular cause during 20 years of follow-up compared to survivors from the same study collective, indicating that cellular TRAF expression may predict cardiovascular long-term outcomes.

Conclusion:
Here, we present the first cross-species assessment of cellular TRAF3, 4 and 7 expression in murine and human atherosclerosis by utilizing a multiparametric approach to circumvent the lack of viable knockout models. Finally, we provide first evidence that cellular TRAF expression assessed by scRNAseq may add to the clinicians armamentarium for MACE prediction in the future.
Abstract 17207: Usefulness of Polygenic Risk Score for Intraventricular Septal Diameter in Patients With Hypertrophic Cardiomyopathy
Authors: Nomura Akihiro , Sato Takehiro , Noguchi Masahiro , Takeji Yasuaki , Tada Hayato , Hayashi Kenshi , Tajima Atsushi , Takamura Masayuki , Fujino Noboru
Published: December 2023

Background:
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant monogenic disease characterized by thickened heart muscles, particularly at the intraventricular septum (IVS), and an increased risk of arrythmias and sudden death. Recently, in addition to monogenic screening, the polygenic risk score (PRS) has been proposed as a potentially useful tool for risk stratification in several cardiovascular diseases. However, it remains unclear whether PRS is also beneficial for risk stratification of patients with HCM.

Methods:
We recruited and genotyped HCM patients from the Kanazawa University Mendelian Disease (KUMD) HCM registry and controls from the KUMD non-HCM familial hypercholesterolemia registry. The PRS was calculated from over 3 million genotyped with imputed variants of each participant for IVS diameter (PRS
IVS
) using a publicly available summary statistic at the National Bioscience Database Center. We assessed the PRS
IVS
distributions among the monogenic HCM, causal variant negative HCM, and control groups. We also tested the associations of PRS
IVS
with the IVS diameters within each group.

Results:
We evaluated a total of 400 participants (267 HCM patients, including 79 with monogenic HCM and 188 with causal variant negative HCM, and 133 controls) for the analyses. Compared to the controls, PRS
IVS
was significantly higher in both monogenic HCM (0.12923 in Monogenic HCM vs. 0.09057 in controls, age- and sex-adjusted p = 0.02) and causal variant negative HCM patients (0.11127 in causal variant negative HCM vs. 0.09057 in controls, p = 9.9x10
-4
). However, no associations were found between PRS
IVS
and IVS diameters in any of the groups.

Conclusions:
In this study, both the monogenic HCM and causal variant negative HCM groups demonstrated significantly higher PRS
IVS
than non-HCM controls. However, we found no evidence to suggest that PRS
IVS
might be useful for risk stratification in patients with HCM.
Abstract 17245: Statin Induced Necrotizing Autoimmune Myositis
Authors: Patel Humail , Vaysblat Michael , Bae Suhwoo , Flescher Andrew , Federbush Matthew
Published: December 2023

Description of Case:
A 64 year old female with hypertension, hyperlipidemia, and type 2 diabetes presented to the emergency room for 3-4 months of progressively worsening bilateral lower extremity weakness with associated edema, but without any reports of pain. The patient had significant impairments in her daily function and now required a cane to ambulate. The patient was found to have significantly impaired strength in the bilateral lower extremities with particular involvement of the proximal thigh muscles. The patient was noted to have a markedly elevated creatine phosphokinase (CPK) to 16,000 and a moderate transaminitis. The patient underwent evaluation with an MRI which revealed several areas of bilateral necrotizing myositis. The patient’s autoimmune markers were remarkable for a positive HMG-CoA reductase antibody and a diagnosis of statin induced necrotizing autoimmune myositis was made. The patient was started on pulse dose steroids without much improvement in her weakness and functional ability. The patient was therefore started on intravenous immunoglobulin with a rapid improvement in her symptoms. The patient was discharged on long term glucocorticoid therapy with appropriate prophylactic medications.

Discussion:
Statin induced necrotizing autoimmune myositis (SINAM) is a very rare form of autoimmune myopathy that is characterized by rapidly progressive proximal muscle weakness along with other potential extramuscular manifestations in the setting of statin use. SINAM should be suspected in any patient on a statin, regardless of duration of treatment, who presents with proximal muscle weakness and a markedly elevated CPK, often > 1000. Treatment, like other forms of autoimmune myopathies, is often centered around immunomodulatory therapies such as high dose glucocorticoids, intravenous immunoglobulin, and long term immunosuppressants. Despite rapid initiation of aggressive treatment, severe forms of the disease have a high mortality as there may be involvement of the respiratory musculature leading to respiratory failure. Given the rarity of this condition, along with the variability in presentation related to the onset of statin therapy, diagnosis and treatment of this entity remains poorly understood.
Abstract 17253: Concepts Associated With 30-day Rehospitalization From Unstructured Data Among Patients With Heart Failure
Authors: Kang Youjeong , Stewart Caden , Stehlik Josef , Shen Jincheng , Gouripeddi Ramkiran , Sideris Konstantinos , Facelli Julio
Published: December 2023

Introduction:
Heart failure (HF) is a diagnosis for which the Centers for Medicare & Medicaid Services mandated public reporting on 30-day risk-standardized rehospitalization rates. Examining risk factors predicting rehospitalization has been widely studied, and most of studies utilized structured data from electronic health records (EHRs) in HF. However, those studies did not use patient-level information that could be captured from unstructured data.

Hypothesis:
Unified Medical Language System (UMLS) concepts that may be used as factors that could be associated with the likelihood of 30-day rehospitalization among patients with HF by using natural language processing technique.

Methods:
We obtained notes from patients diagnosed with HF from EHRs from a tertiary hospital between June 1, 2015 and December 31, 2019. We analyzed 14 note types including physician notes, nursing notes and discharge summaries. We used the publicly available natural language processing software MetaMap to extract UMLS concepts that may be used as factors associated with the liekhood of 30-day rehospitalization and the Pandas package in Python for processing and analysis.

Results:
We identified 350,272 notes among 4,773 patients discharged with HF. The median age of the cohort was 76 years, 54.3% were male, and 89% white, and the 30 day-rehospitalization rate was 12.8%.. A total of 350,272 notes were for 4,164 patients who were not rehospitalized, and 57,212 notes for 609 patients who were rehospitalized. The UMLS concepts identified at a higher rate in notes of rehospitalized patients compared to non-rehospitalized patients included “personal appearance” (7.0% vs 5.5%), “power (psychology)” (3.5% vs 2.5%), and “intrinsic drive” (2.1% vs 1.1%). The UMLS Concepts that were mentioned less in rehospitalized patient notes include “family” (26.3% vs 30.8%), “home environment” (59.9% vs 64%), and “independence” (20.6% vs 24.6%).

Conclusions:
We identified six UMLS concepts associated with 30-day rehospitalization in patients with HF. Further study is warranted to determine whether incorporation of concepts from unstructured data could improve prediction of 30-day rehospitalization and provide opportunities for patient-level intervention.
Abstract 17263: Outcomes and Trends of Percutaneous Coronary Intervention in Nonagenarians With Acute Myocardial Infarction: Results From National Inpatient Sample 2016-2020
Authors: Mehta Shivani , Mittal Vivek , Mir Tanveer , Qureshi Waqas
Published: December 2023

Background:
Acute myocardial infarction (MI) is a leading cause of mortality and morbidity among the elderly. Multiple co-morbidities and advanced age often impede the need for cardiac catheterization in these patients. The literature studying percutaneous coronary intervention (PCI) in nonagenarian patients with acute MI is limited.

Methods:
We examined hospitalized acute MI patients with age 90 or above that were included in the National Inpatient Sample 2016-2020. Acute MI was defined by using the International Classification of Diseases -10. Patients aged less than 90 years were excluded. Outcomes were expressed as percentages. Multivariable logistic regression analysis was used to examine the association of PCI and age 90 or above with primary outcome of mortality, and secondary outcomes [ Figure1]. We also studied the yearly trends of PCI in nonagenarian patients with acute MI patients.

Results:
Of the total hospitalized patients with acute MI (n = 3,120,759), 4.6% (n=142,675) patients were aged 90 years or above. Of these, 9.4% (n= 3,615) died in PCI group and 12.7% (n= 13,215) died in non - PCI group. PCI was performed in 27% (n= 38,430) of the nonagenarian patients with acute MI. The most common outcomes in PCI group were acute heart failure (37.5%), Acute kidney injury (28 %), and atrial arrhythmia (23%). PCI in nonagenarian patients with acute MI was associated with decreased odds of mortality (OR 0.75, 95% CI 0.68-0.82, p value <0.001) and having any of the secondary outcomes (OR 0.74, 95% CI 0.69- 0.79, p value <0.001) [Figure 1]. From 2016-2020, there are increasing yearly trends of PCI in nonagenarian patients with acute MI (p value <0.001).

Conclusion:
Acute MI in elderly patients is associated with significant increased mortality and adverse events. PCI in acute MI patients with age 90 years or above was associated with decreased odds of mortality.
Abstract 17276: NOTCH3-BMPR Interactions Drive Smooth Muscle Cell Proliferation and Medial Hyperplasia in Pulmonary Arterial Hypertension
Authors: Zhang Yu , Puerta Cristian , Hernandez Moises , Thistlethwaite Patricia
Published: December 2023

Background:
One of the characteristics of pulmonary arterial hypertension (PAH) is the proliferation of smooth muscle cells. In heritable PAH, aberrant BMPR2 signaling results in low levels of intracellular ID1. An important pathway involved in vascular smooth muscle cell proliferation and the development of non-heritable PAH is the NOTCH3-HES5 signaling pathway. Previous studies have demonstrated that HES-5 and ID-1 are peptides belonging to the basic helix-loop-helix family, and they act as transcriptional enhancers of cell cycle genes. Transcriptional enhancement or repression requires the heterodimerization of different HES and ID proteins.

Hypothesis:
We hypothesize that HES-5 binds to and degrades IDs in non-heritable cases of PAH.

Methods:
The half-life of ID proteins was assessed in human small pulmonary artery smooth muscle cells that either constitutively expressed or minimally expressed HES-5. In order to understand whether this effect was due to direct binding between HES-5 and ID1, co-immunoprecipitation experiments were performed. Immunofluorescent staining was used to detect the expression level of ID1 and HES-5. Proximity ligation assay (PLA) was utilized to examine of endogenous in-situ interaction of ID1-HES5.

Results:
We found that overexpression of HES-5 significantly diminished the half-life of ID1 and ID3, and had little effect on ID2. All three proteins localized to the nucleus of small pulmonary artery smooth muscle cells. Immunofluorescent staining confirmed elevated levels of HES and reduced levels of ID1 and ID3 in the medial layer of PAH vessels. By PLA assay, we show that HES-5 and ID1 as well as HES-5 and ID-3 physically associate with each other to the level of 40 nanometers.

Conclusions:
Constitutive NOTCH3 signaling and high intracellular HES-5 levels drive vascular smooth muscle cell proliferation in non-familial PAH by binding to and degrading ID intracellular proteins. Our study demonstrates cross-talk between the NOTCH3-pathway and the BMPR2 pathway in this disease, at the level of their downstream effectors: ID1 and HES-5. Further studies should shed light on how these two pathways control the PAH disease process.
Abstract 17284: Prognostic Impact of Silent Cerebral Microbleeds in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Kanzaki Yumiko , Watanabe Tomohiko , Sakane Kazushi , Morita Hideaki , Hoshiga Masaaki
Published: December 2023

Introduction:
Cerebral microbleeds (CMBs) are known to be associated with age, various cardiovascular risk factors, cognitive impairment, the use of antithrombotic drugs, and future neurological or cardiovascular events. Transcatheter aortic valve implantation (TAVR) has emerged as a rapidly evolving treatment for patients with severe aortic stenosis (AS). However, data on CMBs in those patients are scarce.

Hypothesis:
We hypothesized that the presence of CMBs in patients with severe aortic stenosis (AS) undergoing TAVR may be associated with some clinical factors or have prognostic implications.

Methods:
A retrospective analysis was conducted on data from 137 consecutive patients (mean age: 84 ± 5 years, 55 male) with severe AS who underwent T2*-weighted brain magnetic resonance imaging (MRI) prior to TAVR. The brain MRI was assessed by researchers blinded to the patients' clinical information. Additionally, conventional echocardiography was performed to evaluate left ventricular function and valvular abnormalities.

Results:
CMBs were identified in 42 out of 137 patients (31%). No significant differences were observed between patients with and without CMBs in age, gender, serum BNP levels, or antiplatelet/anticoagulant therapy. However, there were significant differences in left ventricular ejection fraction (LVEF) and left ventricular end-systolic volume (LVESV) between the two groups (LVEF: 58 ± 14% vs. 64 ± 10%, p = 0.01; LVESV: 38 ± 25 ml vs. 28 ± 16 ml, p < 0.01, respectively). Over a median follow-up period of 618 days, patients with CMBs had a higher incidence of major adverse cardiac events (defined as death or heart failure re-hospitalization) compared to those without CMBs (24.0% vs. 13.0%, log-rank test, p = 0.04). (Figure).

Conclusions:
Our study reveals a high prevalence of CMBs in patients with severe AS. The presence of CMBs is associated with lower LVEF, increased LVESV, and poor prognosis following TAVR.
Abstract 17286: Ninety-Day Adjudicated Cardiovascular Events in Patients With Covid-19: Association With Vaccination Status and Changes Over Time in the Corona-VTE Network Study
Authors: Bikdeli Behnood , Bejjani Antoine , Khairani Candrika D , Krishnathasan Darsiya , Davies Julia , Porio Nicole D , Tristani Anthony , Armero Andre , Assi Ali , Nauffal Victor , Cambia Umberto , Almarzooq Zaid , Wei Eric , Achanta Aditya , Jesudasen Sirus , Tiu Bruce , Merli Geno J , Leiva Orly , Fanikos John , Sharma Aditya , Vishnevsky Alec , Hsia Judith A , Nehler Mark , Welker James , Bonaca Marc P , Carroll Brett , Lan ZHou , Goldhaber Samuel , Piazza Gregory
Published: December 2023

Background:
Coronavirus disease 2019 (COVID-19) is associated with excess risk of cardiovascular events. Despite the progress in our understanding of cardiovascular complications, uncertainty persists with respect to contemporary event rates, and the association between use of vaccines and outcomes, and changes in incidence rates over time.

Methods:
Adult patients with polymerase chain reaction-confirmed COVID-19 who received care at Mass General-Brigham health system, Beth Israel Deaconess Medical Center, Anne Arundel Medical Center, University of Virginia Medical Center, University of Colorado Health System, and Thomas Jefferson University Health System were included. The Brigham and Women’s Hospital served as the central coordinating center. Clinical events were adjudicated by independent physicians. The primary outcome was 90-day major cardiovascular events, defined as venous or arterial thrombosis, myocarditis or heart failure with inpatient treatment, new atrial fibrillation/flutter, or cardiovascular death. Findings were pre-specified to be assessed separately for patients who were hospitalized with COVID-19 vs outpatients.

Results:
The study included 9,932 patients (03/2020-06/2022, age: 54.8 ± 19.9 years; 55.7% female). Among hospitalized patients, the 90-day cumulative incidence of primary outcome was 15.4 % (95% CI: (14.2-16.7%). Respective 90-day event rates for outpatients were 2.0% (95% CI: 1.3-15.7%) (Figure, Panel A). Cumulative incidence of 90-day outcomes based on vaccination status (restricted to cohort from 12/14/2020 onward) is summarized in Panel B. The change in cardiovascular events over time is represented in Figure, Panel C.

Conclusions:
Adjudicated cardiovascular events are common in hospitalized patients with COVID-19, while the event rates are seven-fold lower among outpatients. Association between vaccination status and outcomes and trends over time require further investigation.
Abstract 17304: Assessing the Nonmedical Needs of Hospitalized Heart Failure Patients: A Qualitative Study
Authors: Palepu Sriram , Damaraju Sarita , Rizaldi Alexandra , Kellogg Audrey , Rakkar Mehtaab , Eberly Lauren A
Published: December 2023

Introduction:
Heart failure (HF) patients experience unexpected hospitalizations, which can cause significant stress. The purpose of this qualitative study was to better characterize the nonmedical stressors during extended hospitalizations for HF patients.

Objective:
This aim of this survey study was to explore the unmet nonmedical needs of patients with HF admitted for an extended stay, focusing on identifying interventions that may enhance patient care and quality of life outside the hospital.

Methods:
A survey was conducted among n=25 HF patients admitted for >5 days to the HF unit at a single institution. We assessed patients’ care gaps at home (e.g. caretakers, food, cleaning, pet care, mental health) and barriers to accessing those gaps. We determined the magnitude of potential impact (MPI) of a category by multiplying the number of people who rated it as stressful and the average level of stress it caused.

Results:
Of the 25 patients, 9 (36%) were female, 13 (52%) were white, and average age was 62.4 ± 13.3 years. Home accessibility (28%), housekeeping (24%), support groups (20%) and HF education (20%) were the most common unmet needs. Housekeeping had the highest MPI, with financial barriers and lack of information as the most frequently reported challenges. Housekeeping, home accessibility (e.g. stair lifts, ramps, rails), support groups, and finding a caretaker were issues identified as having the biggest impact on patient quality of life.

Conclusion:
This study is the first, to our knowledge, to characterize the unmet nonmedical needs of HF patients with extended hospitalizations and highlights possible interventions that may decrease stress and improve quality of life for these patients. The survey results indicate improving access to housekeeping, caretaking, home accessibility, and support groups may reduce patient stress during HF hospitalization. Further research is warranted to explore which interventions are feasible and cost effective.