bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13967: Macrophages Store Low Density Lipoprotein-Delivered Microbial Small RNAs in Lipid Droplets
Authors: Castleberry Mark , Raby Chase A , Allen Ryan M , Linton Macrae F , Vickers Kasey C
Published: April 2024

Low-density lipoproteins (LDL) are causal factors in atherosclerosis. Inflammation is a driving force for both atherogenesis and advanced lesion progression. LDL stimulates inflammation in the lesion; however, the mechanism by which LDL activates macrophages and promotes atherosclerosis inflammation remains to be fully defined. Recently, we reported that LDL is enriched with microbial small RNAs (msRNA) derived from bacteria in the microbiome and environment. Most importantly, we showed that LDL-delivered msRNA activated toll-like receptor 8 (TLR8) in recipient macrophages and inhibition of this pathway reduced atherosclerosis. Nevertheless, the processes by which macrophages store and catabolize exogenous LDL-delivered msRNA are unknown. We

hypothesize that LDL-delivered msRNA is stored in lipid droplets of macrophages

. LDL was found to transport approximately 37μg of total RNA per mg of protein, and macrophages were found to take up LDL-msRNAs through an LDL receptor-independent process (pinocytosis). Confocal microscopy and RNA quantification of purified organelles indicate that macrophage lipid droplets (LD) contain RNA and that LDL treatment increases LD-associated RNA. Macrophages transfected with msRNA fluorescence-labeled (msRNA-Cy5) contain signal in both the organic and aqueous phases after Bligh-Dyer lipid extraction, indicating a potential acyl esterification of the msRNA. To evaluate LDL-msRNA delivery to macrophages
in vitro
, cells were treated with reconstituted LDL (rLDL) loaded with msRNA-Cy5. Utilizing confocal microscopy, rLDL was found to deliver msRNA-Cy5 to macrophages. Ongoing research aims to determine the subcellular processing of LDL-delivered msRNA in macrophages; however, results from microscopy studies support that the endo-lysosome and LD compartments are involved. Moreover, rLDL provides a powerful tool for the study of LDL-msRNA delivery to macrophages by reducing the heterogeneity of lipid cargo that may confound analyses, while enabling the enrichment of specified RNA cargo for cellular delivery. These results support that i) LDL can transfer pro-inflammatory msRNA to macrophages, ii) LDL treatment increases LD-associated RNA, and iii) RNA can be isolated by organic lipid extraction.
Abstract 13982: Evaluation of Electrocardiographic and Intracardiac Electrogram Characteristics for Response to His-Purkinje Conduction System Pacing in Patients With Left Bundle Branch Block Corrected by His Bundle Pacing
Authors: Huang Weijian , Zheng Rujie , Wu Shengjie
Published: April 2024

Introduction:
His-Purkinje conduction system pacing (HPCSP), including His bundle pacing (HBP) and left bundle branch pacing has been proved to improve clinical outcomes in patients with left bundle branch block (LBBB) and heart failure. However, some patients still remain non-responsive to HPCSP. We aimed to evaluate the effect of electrocardiographic and intracardiac electrogram characteristics for response to HPCSP in patients with typical LBBB which could be corrected by HBP.

Methods:
Consecutively enrolled patients with typical LBBB and baseline LVEF ≤40% from January 2012 to June 2020 who were able to achieve LBBB correction during HBP and implanted HPCSP. Baseline QRS duration, paced QRS duration, ΔQRSd, H-QRSend and ΔQRSend/H-QRSend were measured during the implantation. A 1-year absolute increase in LVEF≥15% identified super-response to HPCSP.

Results:
A total of 123 patients were included in the study (mean age 68.2±10.6 years; male 52.0%). Baseline characteristics of patients with ΔLVEF≥15% (N=93) and ΔLVEF<15% (N=30) were comparable except for larger ΔQRSend/H-QRSend (0.42±0.07 vs 0.35±0.08 ms, p<0.001), smaller baseline QRS duration (161.9±15.5 vs 172.3±17.4 ms, p=0.002) and paced QRS duration (100.9±14.9 vs 110.5±13.4 ms, p=0.002) in patients with ΔLVEF≥15%. Receiver-operating characteristic curve analysis demonstrated that a cut-off value of 0.39 for ΔQRSend/H-QRSend presented a sensitivity of 77% and specificity of 76% (AUC=0.776) to predict super-response to HPCSP. At multivariate analysis, larger ΔQRSend/H-QRSend, smaller paced QRS duration and baseline QRS duration remained predictors of super-response after HPCSP.

Conclusions:
HPCSP delivers favorable echocardiographic response in typical LBBB corrected by HBP. A larger ΔQRSend/H-QRSend, smaller baseline QRS duration and paced QRS duration are associated with a better response after HPCSP. ΔQRSend/H-QRSend is a novel and important predictor of LVEF increase.
Abstract 14107: Racial and Income Inequities in Cardiovascular Disease in Cancer versus Non-Cancer Patients: Propensity Score and Machine Learning Augmented Nationally Representative Case-Control Study of Mortality and Cost Among 30 Million Hospitalizations
Authors: Monlezun Dominique , Agrawal Nikhil , Palaskas Nicolas L , Cilingiroglu Mehmet , Marmagkiolis Konstantinos , Dhoble Abhijeet , Arain Salman A , Iliescu Cezar
Published: April 2024

Introduction:
We conducted the first known nationally representative propensity score analysis of racial and income inequities in cardiovascular disease (CVD) for patients with and without active cancer.

Methods:
Propensity score adjusted and backward propagation neural network machine learning augmented multivariable regression was performed by race and income (and their interaction) for the above outcomes in this case-control study of the United States’ largest and first ICD10-coded all-payer hospitalized dataset, the 2016 National Inpatient Sample (NIS). Models were stratified by active cancer and CVD (defined by the 2021 WHO).

Results:
Of the 30,195,722 adult hospitalized patients, 25.64% had CVD, and 7.11% had active cancer. In fully adjusted regression among patients without cancer, Hispanic (OR 1.34, 95%CI 1.03-1.25; p=0.012) and Asian (OR 1.22; 95%CI 1.11-1.34; p<0.001) had significantly increased mortality compared to Caucasian patients as did the lowest (OR 1.11; 95%CI 1.07-1.15; p<0.001) and second lowest (OR 1.05; 95%CI 1.01-1.08; p=0.006) income quartiles compared to the highest. Among patients with cancer, similar significant racial inequities were noted but without income disparities. Mortality was not significantly increased by the interaction in either strata. Among patients without cancer, Hispanics ($14,196.68; 95%CI 12,887.86-15,505.51; p<0.001) and Asians ($19,377.06; 95%CI 17,939.38-20,814.74; p<0.001) had significantly increased costs compared to Caucasians; African American, Hispanic, and Asian patients in the lowest and second lowest income quartiles had significantly increased costs compared to Caucasians in the highest quartile. Patients with cancer had comparable cost inequities by race but not by income or the interaction.

Conclusions:
This nationally representative study suggests that significant income and racial inequities exist in inpatient mortality and cost among patients with CVD, though these disparities are less pronounced among cancer versus non-cancer patients.
Abstract 14111: Feasibility of Therapeutic Ultrasound Delivery for the Treatment of Mitral Stenosis
Authors: Rodriguez Lozano Patricia , Robinson Austin A , Thim Andrew , Zhao Feifei , Xie Yanjun , Dassanayaka Tehan , Miller Paige , Klibanov Alexander L , Kramer Christopher M , Hossack John A
Published: April 2024

Introduction:
Currently, the only disease-modifying therapy for degenerative mitral stenosis (DMS) due to mitral annular calcification (MAC) is open surgical valve repair or replacement, but it is technically challenging, and patients with DMS are often at elevated risk of surgical complications. As such, there is an unmet need for less-invasive strategies to treat DMS. Given the ability of shock-wave grade therapeutic ultrasound to disrupt calcifications, we set out to determine whether therapeutic ultrasound may be a possible treatment strategy for DMS.

Hypothesis:
This study aimed to evaluate whether
ex vivo
histotripsy can produce internal disruption of calcified nodules in the mitral annulus, a precursor to improving valve function in DMS.

Methods:
All experiments were performed on a formalin-fixed human cadaveric heart with severe MAC (Figure 1 A). Histotripsy cavitation was directed at calcified nodules utilizing a sonic concepts HIFUPlex Focused 128 element,1.1MHz array therapy transducer (Figure 1 E). B-mode ultrasound imaging was used to guide therapy. Transducer settings were PRF: 60 Hz, Duty cycle: 8x10^-4, transmit frequency: 1.1 MHz, HIFU Voltage: 60 V, resulting in an estimated pressure output of 34.6 MPa_pk.

Results:
A total of three histotripsy experiments were performed on the primary dominant calcium nodule. Visual assessment of treatment X-ray microtomography (Micro-CT) revealed qualitative fracturing of the calcified nodule from baseline (Figure 1 B), after the first treatment (Figure 1 C), and after three treatments (Figure 1 D). Gross visual inspection and Micro-CT demonstrated no changes to the surrounding fibrous annulus.

Conclusions:
In a feasibility study involving a fixed cadaveric heart, histotripsy therapeutic ultrasound demonstrated the potential to internally disrupt a MAC nodule without injuring the mitral annulus. Further studies are needed to address the ability of histotripsy to improve valve function in DMS.
Abstract 14129: S18 Alleviates The Inflammatory Responses In Interstitial Cells Of Aortic Valves Through Up-regulation Interleukin 37
Authors: Shunyi Li , Jingxin Zeng , Shuwen Su , Kaiji Xie , Xi Yang , Gaopeng Xian , Dingli Xu , Qingchun Zeng
Published: April 2024

Background:
Calcific aortic valve disease (CAVD) is a common cardiovascular disease,which leads to the failure of valvular function in the elderly. CAVD is characterized by complex pathophysiological processes, including inflammation-induced osteoblastic differentiation of aortic valve interstitial cells (AVICs). Anti-CAVD agents with new mechanisms of action are urgently needed. S18 is obtained from a marine-derived Streptomyces strain, and it has a potent anti-inflammatory effect. However, its effect on CAVD is unknown. This study is sought to investigate the role of the natural product S18 in alleviating CAVD progression.

Methods and Results:
Human AVICs treated with LPS showed up-regulation of inflammatory factors ICAM-1, IL-8, and MCP-1, and significant calcification evaluated by Alizarin Red staining. S18 (2 μM) attenuated LPS-induced human AVICs inflammation. RNA-sequencing was used to identify differentially expressed genes (DEGs) in human AVICs treated with LPS or LPS + S18. Transcriptome data indicated the common DEGs enrichment in NF-κB pathway. Further, S18 inhibited phosphorylation of NF-κB induced by LPS. Previous studies suggested that IL-37 is a potential anti-inflammatory target of S18 in AVICs. Knockdown of IL-37 by siRNA exaggerated LPS-induced inflammation, and attenuated the anti-inflammatory effect of S18 on AVICs.

Conclusion:
Our results demonstrate that S18 attenuates LPS-mediated inflammation in human AVICs through inhibiting NF-κB activation, and underlying the mechanism of the anti-inflammatory effect involving up-regulation of IL-37. Our finding provides a novel avenue of preventing the progression of valve calcification.
Abstract 14145: The Ratio Of Hs-ctni/hs-ctnt In Patients With Myocardial Injury Is Associated With Different Clinical Phenotypes
Authors: Chuckaree Ishwar , McDonald Samuel , Diercks Deborah B , Das Sandeep R , De Lemos James A , Vigen Rebecca
Published: April 2024

Introduction:
Hs-cTnI and hs-cTnT concentrations are poorly correlated with a non-linear relationship. The purpose of this study is to determine whether patients with different ratios of hs-cTnI and hs-cTnT are phenotypically distinct.

Methods:
The study included a consecutive patient cohort that presented to a single academic institution between June and July 2020. Only the first admission and the first corresponding pair of troponin values obtained was analyzed. Patients with both hs-cTnI and hs-cTnT
>
99
th
percentile URL (≥ 28 ng/L for hs-cTnI and ≥19 ng/L for hs-cTnT) were categorized based on their hs-cTnT to hs-cTnT ratio (I/T ratio). Patient demographic, clinical characteristics, and adjudicated final diagnoses were compared among tertiles of I/T ratio.

Results:
Of the 809 unique patient encounters, 137 patients had both hs-cTnI and hs-cTnT
>
99% URL. Patients in the lowest I/T tertile were more likely to be male, Black, and have diabetes, hypertension, CKD and CAD. The prevalence of myocardial infarction was 5% with the remaining elevated values secondary to acute or chronic non-ischemic myocardial injury. The adjudicated final diagnosis was more likely to be chronic non-ischemic myocardial injury in the lowest I/T tertile and more likely to be acute non-ischemic myocardial injury in the middle and highest tertiles.

Conclusions:
In this small, single center study, patients with myocardial injury and lower I/T ratio were more likely to have medical comorbidities and chronic myocardial injury as compared to the highest I/T tertile. This suggests that important phenotypic differences exist among patients with abnormal hs-cTnI and T levels.

Table 1. Demographics and clinical characteristics of patient cohort with Hs-cTnI and Hs-cTnT values over 99
th
percentile categorized by tertile of I/T ratio

#Final adjudicated diagnoses defined as per the Fourth Universal Definition of Myocardial Infarction
Abstract 14150: Evaluation of Real-World Long-Term Mortality Following Paclitaxel-Eluting Devices Use in Femoropopliteal Disease Among Veterans
Authors: Maitra Neil , Baig Mariam , Mani Kartik
Published: April 2024

Introduction:
Use of paclitaxel eluting devices have been shown to improve endpoints following femoropopliteal interventions, driven by decreased need for repeat procedures. Post hoc analysis of clinical trials suggest that use of these devices may be associated with increased mortality, without evidence of causation. To assess if relevance of this in usual clinical use, analysis of real-world data is necessary.

Methods:
The Long-term Excess All-Cause Death with Paclitaxel-eluting device in Infrainguinal Peripheral Endovascular procedures - Veterans’ Administration (LEADPIPE-VA) study is a single-center retrospective evaluation of 134 consecutive patients undergoing infrainguinal femoropopliteal interventions from 2010 to 2019 at the Cardiology Division in the St. Louis VA Medical Center.

Baseline Data Age Total DCB Non-DCB p-value<60 11 2 (18.2%) 9 (81.8%) 0.034860-75 92 51(55.4%) 41(44.6%) 0.2971>75 31 17 (54.8%) 14(45.2%) 0.59Mean 71.2 ± 6.6 71.2 ± 6.6 71.2 ± 6.8 0.9527Gender Male 129 67 (51.9%) 62 (48.1%) 0.6598Female 5 3(60%) 2 (40%) Comorbidities HTN 134 (100%) 70 (52.2%) 64 (47.8%) 0.2687DM 82 (61.2%) 41 (30.6%) 41 (30.6%) 0.5147HLD 134 (100%) 70 (52.2%) 64 (47.8% 0.2687Ever smoker 132 (93.9%) 68 (51.5%) 56 (42.4%) 0.1012Current smoker 55 (41.7%) 27 (20.5%) 28 (21.2%) 0.4434CAD 118 (88.1%) 65 (48.5%) 53 (39.6%) 0.0733Carotid disease 45 (33.6%) 28 (20.9%) 17 (12.7%) 0.0999History of MI 95 (70.9%) 56 (41.8%) 39 (29.1%) 0.0404Mean BMI 26.8 ± 5.4 26.7 ± 5.3 26.9 ± 5.7 0.8335Rutherford cl. 3.1 ± 0.6 3.2 ± 0.5 3.1 ± 0.

Results:
Mortality Total Population DCB Non-DCB p-value30-day 4 (3.0%) 0 (0%) 4 (6.3%) 0.04761-year 6 (4.9%) 3 (4.4%) 3 (5.5%) 0.30752-year 16 (16.0%) 10 (10.0%) 6 (6.0%) 0.31543-year 7 (9.9%) 6 (8.5%) 1 (1.4%) 0.01224-year 7 (15.2%) 2 (4.4%) 5 (10.9%) 0.22595-year 2 (6.3%) NA 2 (6.3%)

No significant differences were noted between groups with regards to clinical improvement, repeat interventions, or need for amputation.

Conclusions:
Given the limitation of a small single center retrospective analysis in a real-world population with higher overall complexity, morbidity and mortality, differences between the two groups are small and unlikely to represent a clinical hazard.
Abstract 14153: Novel Tools to Decipher the Molecular Regulation of the Mitochondrial Sodium-Calcium Exchanger, NCLX
Authors: Garbincius Joanne F , Salik Oniel , Mangold Adam S , Makhoul Angelina D , Murray Emma , Lazaropolous Michael P , Tomar Dhanendra , Jadiya Pooja , Elrod John W
Published: April 2024

The precise control of mitochondrial calcium (
m
Ca
2+
) exchange allows the cardiomyocyte to balance the regulation of mitochondrial metabolism against the risk of
m
Ca
2+
overload and cell death. The mitochondrial sodium-calcium exchanger (NCLX) is a major route of
m
Ca
2+
efflux and thus is one of the key proteins that govern
m
Ca
2+
homeostasis. Recent studies have demonstrated that increasing NCLX-dependent
m
Ca
2+
efflux is a promising therapeutic objective for pathologies characterized by deleterious
m
Ca
2+
overload such as ischemia-reperfusion injury, heart failure, and neurodegeneration. A substantial barrier to the development of NCLX-based therapies is that no pharmacologic activators of NCLX are currently available, and indeed, very little is known about the fundamental mechanisms that stimulate or inhibit NCLX activity
in vivo
. Therefore, we generated a plasmid encoding a biotin ligase domain fused to the C-terminus of human NCLX (hNCLX-BioID2HA) and used this construct to perform an
in vitro
proximity biotinylation screen for the unbiased detection of proteins that interact with NCLX and/or modulate NCLX function. We identified ~120 candidate NCLX-proximal mitochondrial proteins in AC16 cardiomyocytes and ~80 in HeLa cells, including several of unknown function. Twenty-five proteins were detected in both data sets, suggestive of conserved function between these two cell types. Current studies are defining the specific molecular function of these mitochondrial proteins and their effects on NCLX expression, NCLX activity, and overall
m
Ca
2+
homeostasis. We are also developing a novel NCLX-3xFLAG knock-in mouse model to enable
in vivo
expression of C-terminal epitope-tagged NCLX under the control of the endogenous murine promoter. We expect this model to aid in overcoming the significant proteomic challenges of manipulating this 13-transmembrane protein. Together, these approaches will help to uncover the post-translational mechanisms that regulate NCLX-dependent
m
Ca
2+
efflux and to identify new therapeutic targets for heart failure and other diseases characterized by disrupted
m
Ca
2+
homeostasis.
Abstract 14155: Exposure to sFlt1-Induced Preeclampsia Enhances the Future Vascular Response to Hypertensive Stimuli in Mice in a Smooth Muscle Mineralocorticoid Receptor Dependent Manner
Authors: Biwer Lauren , Lu Qing , Ibarrola Ulzurrun Jaime , Man Joshua , Carvajal Brigett , Zsengeller Zsuzsanna K , Seely Ellen , Karumanchi Ananth , Jaffe Iris Z
Published: April 2024

Preeclampsia (PE), a syndrome of high blood pressure (BP) and renal damage in late pregnancy, is associated with increased soluble VEGF receptor (sFlt1) and survivors have increased risk of future hypertension with increased angiotensin II (AngII) and salt sensitivity. Since smooth muscle cell mineralocorticoid receptor (SMC-MR) can be activated by hypertensive stimuli, we hypothesized that high sFlt1 exposure during pregnancy may induce a post-partum state of enhanced vascular sensitivity via SMC-MR activation. A PE model was induced by transient viral expression of sFlt1 in pregnant C57Bl6 mice. Elevated serum sFlt1, BP and glomerular endotheliosis was confirmed which all resolve post-partum. Two months later, resistance arteries from post-PE mice show no change in vasoconstriction to AngII but with increased mRNA ratio of the pro-constrictive AngII receptor-1(ATR1) to the vasodilatory ATR2. In a small cohort of women with prior PE, we confirm salt sensitivity of BP thus, postpartum mice were implanted with telemetric BP monitors and exposed to high salt or AngII (600mg/kg/day) infusion. Mice with prior PE had a significantly increased BP response to hypertensive stimuli. Microvessels from mice after PE and hypertensive stimuli had enhanced
ex vivo
myogenic tone and AngII vasoconstriction. To test the direct impact of sFlt1 on SMC-MR function, cultured SMC (Pac1) were transiently exposed to sFlt1 (24 hours on then off) to mimic the post-PE state. SMC-MR transcriptional activity in response to aldosterone and AngII were significantly increased after sFlt1 exposure as measured by luciferase reporter assay. SMC-MR activation and target gene expression was also enhanced after sFlt1 exposure (including AT1R/AT2R ratio). Finally, the role of SMC-MR in the post-PE phenotype was tested in vivo by PE induction in SMC-MR-KO vs MR-intact littermates. Post partum, SMC-MR-KO mice were protected from the PE-induced increase in aortic stiffness, microvascular myogenic tone and AngII vasoconstriction. sFlt1-induced PE produces a state of enhanced sensitivity to AngII that may be mediated by increased activation of SMC-MR. These data support the use of MR antagonists to mitigate the increased risk of cardiovascular disease in women exposed to PE.
Abstract 14160: Trends in Racial and Ethnic Differences in Adiposity and Association With All-Cause Mortality in Adults in the United States: A 20-year National Health and Nutrition Examination Survey Analysis, 1999-2018
Authors: Lu Yuan , Liu Yuntian , Caraballo Cesar , Massey Daisy , Mahajan Shiwani , Herrin Jeph , Krumholz Harlan M
Published: April 2024

Introduction:
Reducing overall rates of and the racial/ethnic differences in obesity is a public health priority in the US. However, it is unknown how the racial/ethnic differences in different adiposity measures changed in the US population over recent decades

Methods:
Using data from the National Health and Nutrition Examination Survey 1999-2018, we determined trends in the racial/ethnic differences of several adiposity measures and whether race/ethnicity moderates the associations between these measures and all-cause mortality. Adiposity measures included overweight (body mass index [BMI] of 25.0-29.9 kg/m
2
), overall obesity (BMI ≥30.0 kg/m
2
), abdominal obesity (waist circumference [WC] ≥88 cm for women or ≥102 cm for men), and high body fat (body fat mass percentage [FM] ≥35% for women or ≥25% for men).

Results:
The study included 49,629 adults aged 18-79 years (mean age 45.3 [SD, 17.9] years, 51.3% women), of whom 12.5% were Black, 15.5% were Latino/Hispanic, and 72.0% were White. Between 1999 and 2018, Latino/Hispanic people had a higher prevalence of overweight, overall obesity, abdominal obesity, and high body fat than White people. The gaps between Latino/Hispanic and White people significantly increased for all adiposity measures (P<0.01 for all measures) during this time. Black people had a higher prevalence of overweight, overall obesity, and abdominal obesity, but a similar prevalence of high body fat compared with White people. There were no significant changes in the gaps between Black and White people for any adiposity measures. For all adiposity measures, the associations between adiposity measures and mortality did not differ by race/ethnicity.

Conclusions:
Racial/ethnic differences in the prevalence of overweight, overall obesity, abdominal obesity, and high body fat persisted or increased over 20 years, with the differences increasing between Latinos/Hispanics and Whites and not changing between Blacks and Whites.
Abstract 14162: Impact of Migraine Headaches on Stress Induced Takotsubo Cardiomyopathy
Authors: Varghese Jobin J , Yacob Omar , Garcia-Garcia Hector
Published: April 2024

Introduction:
Takotsubo cardiomyopathy (TTC) is an acute process, characterized by ventricular dysfunction, typically due to a neuro-cardiogenic mechanism. Although many stressors have previously been identified and can precipitate TTC, there have been no reports citing the association or effects of migraines attacks.

Hypothesis:
Migraines predispose a protective effect on TTC patients

Methods:
We conducted a US-wide analysis of TTC hospitalizations from 2013 to 2017 by querying the National Inpatient Sample database. Patients admitted with a principal diagnosis of TTC with a history of migraines were identified using the ICD-10 codes. TTC patients with migraines were then compared to TTC patients without migraines regarding mortality and acute inpatient complications (intubation, cardiac arrest, heart failure exacerbation, acute kidney injury). A logistic regression model was constructed to account for potential confounders.

Results:
A total of 172025 TTC patients were identified, of those patients, 3610 were found to have suffered from migraines. After accounting for potential confounders, TTC patients with a diagnosis of migraine were associated with a lower odds for mortality (OR: 0.388; [0.311-0.485]; p <0.001) and acute complications (OR: 0.511 [0.471-0.554]); p <0.001) compared to those without migraines. In terms of mortality, the presence of acute complications had the highest odds for mortality (7.830 [7.439-8.240]; p <0.001), followed by cerebrovascular disease, cancer, and age. Depression, Diabetes, smoking, and obesity were associated with a decreased odds for mortality.

Conclusions:
TTC patients with migraines were associated with lower mortality and better inpatient outcomes.
Abstract 14183: Oxidized Phospholipids Promote NETosis and Arterial Thrombosis in LNK(SH2B3) Deficiency
Authors: Dou Huijuan
Published: April 2024

Background and Objective:
GWAS have shown association of a common SNP (R262W) in
LNK
with neutrophilia, thrombocytosis and coronary artery disease (CAD). We have shown that LNK(R262W) reduces LNK function and that LNK deficient mice display prominent platelet-neutrophil aggregates, accelerated atherosclerosis and thrombosis. Platelet-neutrophil interactions can promote neutrophil extracellular trap (NET) formation. The goals of this study were to assess the role of neutrophil extracellular traps (NETs) in atherosclerosis and thrombosis in mice with hematopoietic
Lnk
deficiency and to evaluate the role of LNK in atherothrombosis in humans and mice bearing a gain of function variant in JAK2 (JAK
V617F
).

Methods and Results:
We bred mice with combined deficiency of
Lnk
and the NETosis-essential enzyme peptidylarginine deiminase4 (PAD4); their bone marrow was transplanted into Ldlr-/- mice. There was accelerated carotid artery thrombosis with prominent NETosis in
Lnk
deficient mice with complete reversal by PAD4 deficiency. In contrast, PAD4 deficiency abrogated increased NETosis in plaques but did not alter plaque size or morphology. Thrombin-activated
Lnk
-/-
platelets promote NETosis when incubated with
Lnk
-/-
neutrophils compared to WT platelets or WT neutrophils. This involved increased surface exposure and release of oxidized phospholipids (oxPL) from
Lnk
-/-
platelets, as well as increased priming and response of
Lnk
-/-
neutrophils to oxPL. To counteract the effects of oxPL, we introduced a transgene expressing the single-chain variable fragment of E06 (E06-scFv). E06-scFv reversed accelerated NETosis, atherosclerosis and thrombosis in
Lnk
-/-
mice. Using data from UK Biobank we showed that individuals with the JAK2
VF
mutation only showed increased CAD when also carrying the LNK R262W allele. Mice with hematopoietic

Lnk
+/-

and

Jak2
VF

clonal hematopoiesis, showed accelerated arterial thrombosis but not atherosclerosis compared to

Jak2
VF
Lnk
+/+

controls.

Conclusions:
Increased NETosis in hematopoietic LNK deficiency promotes arterial thrombosis in an oxPL-dependent fashion. Reduced LNK function may increase CAD in humans carrying JAK2
VF
mutations possibly reflecting increased arterial thrombotic risk.
Abstract 14186: A Regional, Multidisciplinary Program to Streamline and Track Care of Aortic Dissection Patients
Authors: whippo beth , Chia Matthew C , schroeder jennifer , Kolek Jessica , Mehta Christopher K , Vassallo Patricia , Malaisrie S. Christopher , Hoel Andrew W
Published: April 2024

Introduction:
Acute aortic dissection (AAD) represents a medical emergency warranting management by multiple medical and surgical specialties. These specialties contribute unique expertise to the management of both immediate and long-term needs for patients with AAD. We hypothesize that coordinated, multidisciplinary care tracked using an automated dashboard can improve care for patients with AAD.

Methods:
This was a single-center, retrospective analysis of all AAD from February 2018 through April 2021. Clinicians from cardiology, cardiac and vascular surgery worked with administrative leadership to develop the program to streamline the coordinated care of patients with AAD. Concurrently, a provider-facing dashboard was developed to track volume and program performance using automated data abstraction from the institutional Enterprise Data Warehouse. Data elements included patient demographics, comorbidities, clinical data on dissection treatment and patient outcomes. These elements were compared in a pre-/post- design after the launch of the dashboard (Jan 20) using the Fisher exact test, the Kaplan-Meier method, and the log-rank test.

Results:
238 patients were treated for AAD during the study period, with 134 patients prior to the program’s launch and 104 patients after. These included Stanford Type A and B dissections, which were similarly distributed pre-/post- period (p = 0.69). After the launch of the program outcome metrics improved (figure 1). Overall survival was similar at one (88.7% vs 84.8%, p = 0.36) and three months (85.5% vs. 82.3%, p = 0.46)

Conclusions:
Patients with AAD have complex care needs involving multiple specialties. Despite limited long-term follow up after program implementation, our results demonstrate the feasibility of tracking a comprehensive aortic care program with an automated dashboard. Combining multidisciplinary care with robust analytic support may improve the longitudinal care of these patients.
Abstract 14208: Annexin A5 Inhibits Endothelial Inflammation Induced by Lipopolysaccharide-Activated Platelets and Extracellular Vesicles
Authors: Tschirhart Brent J , Lu Xiangru , Feng Qingping
Published: April 2024

Introduction:
Sepsis is a leading cause of death worldwide with no targeted therapeutics available. Sepsis results from a dysregulated immune and inflammatory response. During sepsis or lipopolysaccharide (LPS) stimulation, platelets are activated, and release procoagulant/proinflammatory membrane-derived extracellular vehicles (EVs). Our previous studies show recombinant human annexin A5 (Anx5), a phosphatidylserine-binding protein, inhibits inflammation and improves survival in endotoxic mice, a model of sepsis.

Hypothesis:
Anx5 will block the pro-inflammatory response induced by LPS-activated platelets and EVs in vascular endothelial cells (ECs).

Methods:
ECs were cultured from adult C57BL/6 mice. Platelets and EVs were activated by LPS and added to ECs for four-hours with/without AnxA5. Inflammatory cytokines and adhesion molecule expression was quantified in ECs using RT-qPCR. Endothelial monolayer structural integrity was measured in septic conditions using trans-endothelial electrical resistance (TEER). Monocytes were added to LPS-treated ECs and adhesion was quantified via brightfield microscopy.

Results:
Supplementation of annexin A5 (1 μg/ml) on ECs treated with LPS-activated platelets and EVs reduced the expression of inflammatory cytokines and adhesion molecules on ECs when compared to ECs treated with LPS (1 μg/ml) activated platelets and EVs alone. In septic conditions, endothelial monolayers that were treated with annexin A5 had a higher TEER compared to the monolayers without annexin A5, indicating that annexin A5 preserved endothelial monolayer structural integrity in septic conditions. Annexin A5 treated ECs also had significantly less monocytes adhesion in septic conditions when compared to ECs treated without annexin A5.

Conclusions:
The proinflammatory response induced by activated platelets and EVs is inhibited by Anx5. The ability to maintain the structural integrity of endothelial monolayers and reduce monocyte adhesion during septic conditions, makes Anx5 a promising treatment option for sepsis.
Abstract 14221: The Role of Left Ventricular Dysfunction in Children With Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Howell Alison J , Jeewa Aamir , Nicholson Dawn , Jean-st-michel Emilie M , Minn Eric
Published: April 2024

Introduction:
We sought to evaluate the impact of left ventricular dysfunction (LVDfx) in children with a definite arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis.

Methods:
We retrospectively reviewed patients 0-18 years of age diagnosed with ARVC at our institution between 2001-2018. Patients with LVDfx, defined as an ejection fraction of <55% on echocardiogram, were identified and their outcomes compared to ARVC patients without LVDfx. Kaplan-Meier transplant-free survival curves were utilized.

Results:
Thirty-five children with a diagnosis of ARVC were identified. Twelve patients (34%) had LVDfx, of which 7 (20%) had moderate-severe LVDfx. The median age at diagnosis was 15 years (IQR 13.2 - 15.8) with a median follow-up time of 2.1 years (IQR 1.1 - 4.3). There was no association with increased left ventricular dimension or mitral regurgitation in either group. Cardiac magnetic resonance imaging demonstrated that LVDfx was associated with moderate to severe right ventricular dysfunction (41.6% vs 17.4% p = 0.009) and late gadolinium enhancement (58.3% vs 8.7% p = 0.004). Arrhythmia burden was greater in the LVDfx group with a higher incidence of ectopy (83% vs 50% p = 0.04) and non-sustained ventricular tachycardia (83% vs 22% p = 0.0009). The LVDfx group was significantly more likely to receive an angiotensin converting enzyme inhibitor (41.6% vs 0% p = 0.002) or a beta-blocker (75% vs 8.7% p = 0.0001). Total length of hospital stay was significantly longer in the LVDfx cohort (median 2 days vs 0 days p = 0.001). The two-year transplant free survival was significantly worse in the LVDfx group (88% vs. 100%, p=0.04, figure 1).

Conclusions:
ARVC is not always confined to a single chamber and LVDfx confers a greater risk to the healthcare trajectory of children with ARVC. Therapeutic strategies for LVDfx may have a substantial impact on outcomes in this population.
Abstract 14238: A Real-World Comparison of Percutaneous Coronary Intervention vs Coronary Artery Bypass in Patients With Chronic Total Occlusion
Authors: Khan Mahin , Tanveer Ud Din Mian , Roomi Sohaib , Ullah Waqas , Virani Salim S , hamzeh ihab , Khalid Mirza , Birnbaum Yochai , Alam Mahboob
Published: April 2024

Introduction:
There is a paucity of data comparing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with chronic total occlusion (CTO) of the coronary arteries.

Methods:
The National Inpatient Sample (NIS) database was queried to identify all CTO related hospitalizations from 2002-2018. Patients undergoing PCI were compared with those having CABG for CTO using Cochran-Mantel-Haenszel statistics to determine unadjusted odds ratios (OR). A propensity matched analysis (PSM) was used to determine adjusted OR for major in-hospital outcomes.

Results:
A total of 404,563 patients with CTO were included in the analysis. Of these, 20,841 (5.6%) patients underwent CABG whereas 383,722 (94.8%) underwent PCI. Patients in the PCI group had a higher percentage of chronic obstructive pulmonary disease, diabetes, coagulopathy, obesity and renal failure. On an unadjusted analysis, the primary outcome of in-hospital mortality was comparable between the two groups. The odds of stroke, acute kidney injury, sepsis, major bleeding and need for IABP were higher with CABG, whereas the odds of cardiopulmonary arrest and coronary artery dissection were higher with PCI. On a propensity adjusted analysis, PCI was associated with a higher mortality and comparable rate of major bleeding and sepsis compared to CABG (Table). CABG, however, had a higher hospitalization cost ($ 156113.03 vs. $ 103078.48, p=<0.0001), and a mean length of stay (8.93 vs. 4.82 days, p=<0.0001) as compared to PCI.

Conclusions:
Our findings show that CABG has a lower inpatient mortality for CTO as compared to PCI, however it is associated with increased risk of complications, higher cost and increased length of hospitalization, highlighting the need for randomized data on the subject.
Abstract 14242: Reverse Remodeling After Catheter Ablation- A Single Center Retrospective Analysis
Authors: Aedma Surya K , mahajan pranav , Jadav Raja S , Naik Anant , Gadela Naga Vaishnavi , Garg Anuj , Kocheril Abraham G
Published: April 2024

Introduction:
The presence of supraventricular tachyarrhythmia (SVT) causes structural and functional changes over a period. The aim of our study is to assess the changes in structural and functional echocardiographic parameters following cardiac catheter ablation (CA) for SVT to see if correction of arrhythmia and restoration of sinus rhythm using CA leads to reverse remodeling.

Methods:
A single center retrospective analysis was performed on patients undergoing CA for SVT between January 2019 and April 2020. Pre- and post-ablation left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left atrial volume index (LAVI), left atrial dimension (LAD), left ventricular ejection fraction (LVEF) and left ventricular wall thickness were measured. The cohort was sub-grouped into arrhythmia free (AF) and arrhythmia recurrence (AR) patients. Paired student’s t test was performed to compare mean volumes and differences in pre- and post-ablation parameters amongst AF and AR patients.

Results:
51 (67.1%) out of a total of 76 patients were AF and 25 (32.9%) had AR based on electrocardiogram done at or around the time of post- ablation echocardiogram. In AF patients there was a statistically significant decrease in post-ablation LVEDV, LVESV, LAVI, and LAD [LVEDV: Post-117 vs Pre- 124 (p=0.002), LVESV: 59 vs 67 (p=0.002), LAVI: 34 vs 38 (p=0.034), and LAD: 3.9 vs 4 (p=0.006)] and increase in LVEF [51 vs 49 (p=0.004)], whereas AR patients had higher post-ablation volumes [LVEDV: 118 vs 108 (p=0.015) and LVESV: 53 vs 50 (p=0.0001)]. [Figure 1]

Conclusions:
Our findings were significant for decreases in LVEDV, LVESV and LAVI following successful CA of SVT indicating reversal of cardiac remodeling. Importantly, there was an improvement in LVEF. Our study indicates that CA and restoration of sinus rhythm causes improvement in ejection fraction and is important to consider early CA to treat patients in heart failure from tachyarrhythmias.
Abstract 14243: The Apelin Mimetic Peptide (2Nal) Partially Inhibits the Transient Outward Potassium Current (Ito) in Rat Cardiomyocytes; a Potential Pharmacological Agent Against Brugada Syndrome
Authors: Contreras Vite Juan Antonio , Murza Alexandre , TRAN Kien , Sarret Philippe , Auger-messier Mannix , Lesur Olivier , Marsault Eric , Dumaine Robert
Published: April 2024

Introduction:
Brugada syndrome (BrS) is an inherited disease characterized by ventricular cardiac arrhythmias leading to sudden cardiac death. One potential cause for arrhythmias is a disruption of the balance between the depolarizing fast sodium inward current (I
Na
) and its opposing transient outward currents (I
to
) favoring a faster repolarization during phase one of the action potential (AP).

Hypothesis:
BrS is mainly associated with a reduction in I
Na
amplitude caused by dominant mutations in the gene SCN5A encoding cardiac sodium channels. However, recent studies have shown that gain-of-function mutations in KCND3, the gene encoding Kv4.3 channels, increase I
to
amplitude. Therefore, targeting I
to
to modulate the balance of current during phase one of the AP represents a promising therapeutic approach to BrS,

Methods:
We used Patch-Clamp technique to test the effect of 2Nal, a newly synthesized peptide derived from apelin, on I
to
in rat ventricular cardiomyocytes. Apelin is an endogenous neurotransmitter with strong inotropic effects on cardiac cells.

Results:
We found that apelin had no effect on I
to
. In contrast, 2Nal maximally inhibited 46.9% ± 3.4 (n=9) of I
to
with an IC
50
=0.29 nM but did not change its kinetics, thus indicating that 2Nal acts as a partial blocker. The voltage dependence of potassium channels availability was not modified, suggesting that 2Nal simply reduced the conductance of each channel contributing to I
to
.

Conclusions:
Because of its partial antagonist effect on ITo, 2Nal provide a safety margin that could be potentially useful for the treatment of Brugada syndrome.
Abstract 14247: Myocardial Histopathology In Atrial Cardiomyopathy
Authors: Ruohonen Ilkka , Eranti Antti , Sinisilta Sami , Lahtinen Veikko , Relander Arto , Jalkanen Sirpa , Airaksinen Juhani , Jalkanen Juho M , Gunn Jarmo , Hollmen Maija , Kiviniemi Tuomas O
Published: April 2024

Background:
Atrial cardiomyopathy (ACM) is characterized by multiple histopathological features but the entity lacks systematic validation.

Objectives:
We sought to correlate atrial histopathology with clinical characteristics of patients with ACM and AF and outcomes following cardiac surgery.

Methods:
The pathological findings of the atrial myocardial biopsies from 178 patients who underwent any cardiac surgery between 2016-2018. Atrial cell nuclear structure and morphology, myocyte hypertrophy and interstitial fibrosis were graded and analyzed quantitatively. Study population was divided in three groups based on preoperative ECG: 1) patients in sinus rhythm with no signs of ACM (P wave duration <120ms)(SRn); 2) patients in sinus rhythm and ACM (P>=120 or biphasic waves in inferior leads)(SRa); and 3) atrial fibrillation (AF).

Results:
SRa patients had decreased number of nuclei/area and smaller total cardiomyocyte area compared to SRn patients (p=0.04 forboth). Patients with AF had bigger, less solid and circular nuclei compared to SRn patients (p<0.01 for all). AF patients had increased area of interstitial fibrosis (p<0.01) compared to SRn patients.

Conclusions:
Histopathological characteristics of ACM include changes in nuclear chromatin structure.
Abstract 14261: Catheter Ablation of Atrioventricular Nodal Reentrant Tachycardia: A Standardized Mapping System Protocol
Authors: Bulian Francesca , Manfrin Massimiliano , Rauhe Werner
Published: April 2024

Introduction:
according to European guidelines, ablation has become the treatment of choice in patients with symptomatic atrioventricular nodal reentry tachycardia (AVNRT). Despite the high procedure success rate, anatomical variations can affect the outcome in terms of relapses and complications. As recently demonstrated, low-voltage bridge visualization allows low pathway identification and therefore a new ablation strategy.

Hypothesis:
our purpose was the validation of standardized ablation protocol within the low-voltage bridge area.

Methods:
70 consecutive patients with inducible AVNRT were evaluated and a three-dimensional voltage map of the right atrial septum and Koch Triangle was constructed by means of contact mapping. Ablation site was identified as the low-voltage area below the His bundle, adjusting the high-voltage slider to 1,5 mV and dynamically adjusting the slider of low-voltage. Radio-frequency energy (with an average number of nine lesions per patient) was then delivered within this area until the appearance of junctional beats. The results were tested at the end of the procedures and during the observational period (the mean follow-up was 10,5 months).

Results:
the slow pathway was identified by the low-voltage bridge in 60 patients (85,6%) and in these patients, the target lesions in that area finally prevented induction of AVNRT in 100% of cases. A zero-fluoroscopy approach was possible for 50 patients (83%). Compared with standard AVNRT ablation, no complications as well as no statistical differences in terms of total procedure time were observed (p=0,056). 59 patients (98%) had no relapses during the follow-up.

Conclusions:
voltage gradient mapping successfully targeted the slow pathway in most of our cases. Lesions on the voltage bridge led to effective ablation of AVNRT and to a drastic x-ray exposure reduction in the absence of acute or long-term complications.
Abstract 14285: Plasma Proteomic Profiling of Endurance Exercise Identifies Changes in Extracellular Matrix Biology Associated With Adaptations in Maximal Oxygen Uptake
Authors: Robbins Jeremy , Rao Prashant , Mi Michael , Keyes Michelle , Deng Shuliang , Katz Daniel H , Jean Beltran Pierre M , Tahir Usman A , Barber Jacob , Farrell Laurie , Clish Clary , Sarzynski Mark A , Bouchard Claude , Gerszten Robert E
Published: April 2024

Introduction:
Proteins are important regulators of cardiometabolic health that are increasingly recognized as being modulated by exercise.

Hypothesis:
We measured approximately 5,000 plasma proteins before and after an endurance exercise training (ET) program to test the hypothesis that proteomic changes are related to adaptations in maximal oxygen uptake (
Δ
VO2max) and long-term health outcomes.

Methods:
We applied an affinity-based proteomics platform before and after ET in 654 sedentary participants (mean age = 35, 35% black) from the HERITAGE Study. Subjects performed graded cycle ergometry, exercising at 75% VO2max, 3x/week over the final 6 weeks of a 20-week program. Changes in plasma protein levels after ET were determined using paired
t
tests. Multivariate linear regression assessed the relationship between
Δ
protein and
Δ
VO2max after ET. Statistical significance was determined using a false discovery rate (FDR)
<
0.05. Multivariate cox proportional hazards regression estimated hazard ratios (HR) of protein levels and all-cause mortality in the Framingham Heart Study (FHS) and Malmo Diet and Cancer Study (MDCS).

Results:
455 proteins changed after ET, including 306 proteins that increased. Proteins related to the extracellular matrix (ECM) were overrepresented among biologic processes and pathways in enrichment analyses. Absolute changes in five proteins after ET were related to ΔVO2max [FTH1: (β = -31.8, q = 0.009), CDH5 (β = 28.3, q = 0.028), FAP (β = 28.0, q = 0.025), ANGPT2 (β = 28.1, q = 0.028), PRELP (β = 26.6, q = 0.044) after adjustment for age, sex, race, BMI, and baseline VO2max. Fibroblast activation protein (FAP), was positively associated with baseline VO2max (β = 43.6, p = 0.02) and inversely related to all-cause mortality in FHS and MDCS (HR = 0.84 and 0.86, p = 0.0002 and 0.004, respectively).

Conclusions:
Endurance exercise leads to large-scale plasma proteomic changes, including increased levels of ECM-related proteins. Several novel proteins modulated by ET were associated with
Δ
VO2max, including FAP, a serine protease relevant in wound healing and metabolism that is inversely associated with mortality in two separate cohorts. External validation and additional efforts to understand FAP’s mechanistic relevance are warranted.