bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 129: A Systemic Proteomics Analysis Identifies Energy Generation Pathways That Characterize The Vulnerability Of Brain And Kidney As Compared To Heart And Liver After Cardiac Arrest
Authors: Shoaib Muhammad , Choi Jin-woong , Hayashida Kei , Choudhary Rishabh , Miyara Santiago , Baek Seunguk J , Curtin Patricia M , Becker Lance B , Lee Ju Yeon , Kim Junhwan
Published: June 2023

Background:
Substantial organ dysfunction and dynamically altered physiology is observed after whole-body ischemia-reperfusion injury resulting from cardiac arrest (CA) and resuscitation. There are limited therapeutic interventions available because this disease process is complex, and the pathophysiology is poorly understood. By understanding the dynamic alterations in the proteome of the brain, heart, kidney, and liver following CA and resuscitation, we can better characterize the underlying disease mechanisms in order to identify novel therapeutic targets.

Methods:
Male Sprague-Dawley rats underwent 20 min asphyxial-CA and resuscitation via cardiopulmonary bypass. Brain, heart, kidney, and liver tissues were harvested post-CA or post-resuscitation. Protein levels in these tissues were analyzed by cutting-edge proteomics analysis. We then performed a thorough bioinformatics analysis at the organ, organelle, and pathway levels to assess the pathologic state of each organ following CA and resuscitation.

Results:
The total number of proteins identified and quantified were 3411, 1928, 2731, and 2879 in the brain, heart, kidney, and liver, respectively. Statistical analysis revealed that the brain and liver showed more significant overall alterations than the heart and kidney after CA. Resuscitation significantly normalized the proteomic alterations in the heart and liver but not in the brain and kidney. Among many essential metabolic pathways altered, such as amino acid biosynthesis or lipid metabolism, proteins that participate in oxidative phosphorylation, the key energy generating pathway, were substantially altered in the brain and kidney. Furthermore, proteins related to glycolysis, another major energy generating pathway, were also significantly altered in the brain.

Conclusions:
The differential proteome alteration after global ischemia-reperfusion post-CA and resuscitation emphasizes the vulnerability of brain and kidney in their failure to restore energy generating pathways in contrast with the resilience of heart and liver. The novel informatics analysis provides mechanistic insights into the pathologic state of major organs and provides potential therapeutic targets to improve outcomes after CA.
Abstract 12906: Exercise Training Protects Against Ischemic Muscle Damage in a Large-Animal Model of Peripheral Artery Disease
Authors: Fletcher Emma , Ismaeel Ahmed , Papoutsi Evlampia , Li Feifei , Hoffmann Carson , Sasaki Maiko , Zarge Joseph , Brewster Luke P , Koutakis Panagiotis
Published: June 2023

Peripheral artery disease (PAD) causes an ischemic myopathy in the lower extremity muscles, which contributes to patient functional disability. Although structured exercise therapy is a leading therapeutic to improve ambulatory function, the impact of exercise on PAD myopathy is unclear. Using our porcine model of PAD, we sought to elucidate the effect of hindlimb ischemia on markers of 1) muscle damage (caspase 3, myogenic differentiation 1 (MyoD), and Forkhead box protein O1 (FOXO1)), 2) muscle protein turnover (autophagic flux and proteolytic activity), and 3) whether these indices were altered with exercise training.

Methods:
Seven Yorkshire swine were exposed to right hindlimb ischemia by endovascular external iliac artery occlusion. Following ischemia onset, the swine were divided into 2 training groups: supervised exercise trained (ET) (n=4) and sedentary controls (SED) (n=3). ET pigs followed an incremental treadmill protocol 3 times weekly for 4 weeks. SED pigs had standard ambulation. The tibialis anterior from ischemic and non-ischemic limbs was excised after animal termination. Markers of muscle damage and proteolytic activity were assessed via RT-PCR and enzymatic activity kits, respectively. The ratio of intramuscular microtubule-associated protein light chain 3 (LC3)-II:LC3-I, as well as sequestosome (p62), and mitofusion2 (MFN2) content from immunoblots were used to monitor autophagic flux.

Results:
Gene expression of intramuscular damage was significantly higher in SED ischemic muscle compared to ET muscle (caspase 3 (SED: 5.59±1.5; ET: 1.67±1.5), MyoD (SED: 4.55±1.2; ET: 1.24±1.5) and FOXO1 (SED: 1.74±0.5; ET: 1.07±1.1), p<0.0001). Moreover, ischemic muscle from ET pigs showed no alteration in markers of muscle damage when compared to the SED and ET non-ischemic conditions (p>0.05). Although proteolytic activity was unaltered (p>0.05), autophagic flux tended to be increased in ET ischemic muscle (LC3-II:LC3-I ratio (ET: 0.21±0.1; SED: 0.10±0.1 AU, p=0.099), p62 (ET: 15.80±5.1; SED: 7.75±2.8 AU, p=0.068) and MFN2 (ET: 42.72±15.9; SED: 16.82±11.3 AU, p=0.214).

Conclusions:
These data suggest exercise therapy is protective against ischemic muscle damage and may improve muscle quality via accelerating autophagic flux.
Abstract 12931: Contemporary Trends of Subcutaneous Implantable Cardioverter Defibrillator Utilization in the United States: Insights From the National Inpatient Sample 2016-2019
Authors: Shatla Islam , El Iskandarani Mahmoud , kennedy kevin , Wimmer Alan P
Published: June 2023

Introduction:
The subcutaneous implantable cardioverter defibrillator (S-ICD) has emerged as an alternative to the transvenous ICD with comparable efficacy and complication rates in clinical trials. Adoption of this technology and real-world clinical experience are less well described.

Methods:
This was a retrospective descriptive cohort study using data from National Inpatient Sample (NIS) for calendar years 2016-2019. Outcomes were cardiovascular adverse events, all-cause mortality, 30-day readmission, and resource utilization in patients who had S-ICD implantation.

Results:
We identified 6655 patients who had S-ICD implantation between 2016-2019. S-ICD implant rates remained between 10-12% of total ICD implants in the US over the study period (Figure 1a), though hospital implant rates were widely distributed (Figure 1b). The mean (SD) age of the population was 56.1 ± 15.9 years, and 2002 patients (30.1%) were female. Median length of stay (IQR) was 6.0 (4.0, 10.0). Hospitalization costs were $ 245937.1 ± 206047.3. Adverse cardiovascular events associated with the hospitalization were: pericardial perforation/cardiac tamponade (0.2%), hemothorax/pneumothorax (1.1%), stroke/TIA (0.5%), cardiogenic shock (8.6%), cardiac arrest (11%), and vascular complications (1.3%). A total of 48 patients (0.7%) died. Non-elective readmission within 30 days post-procedure occurred in 15.7% of cases.

Conclusion:
S-ICD implant rates were stable over time but varied widely among hospitals. Hospitalization-associated adverse cardiovascular events may be more a reflection of the vulnerable population undergoing S-ICD implant than risk of the procedure.
Abstract 12932: Should We Screen For Radiotherapy-Induced Heart Disease With Exercise Stress Echocardiography? Emphasis on Major Adverse Cardiac Events
Authors: Toro-Manotas Rafael , Mogollon Renzo , Garcia-Arango Mariana , Vallejo Bryan , Carroll Jamie L , Hoppenworth Jenna , Thicke Lori , Smith Deanne D , Klassen Christine L , Haddad Tufia , Peethambaram Prema P , Mutter Robert , Stan Daniela , Villarraga Hector R
Published: June 2023

Introduction:
Exercise Stress Echocardiography (ESE) is recommended as a screening tool for the evaluation of Coronary Artery Disease (CAD) in patients with suspected Radiation-Induced Heart Disease (RIHD). Up to now, studies have only evaluated its association with the extent of CAD.

Hypothesis
Cancer survivors treated with chest Radiotherapy (RT) that undergo an ESE and have a +ESE develop more MACE than those who have -ESE.

Methods:
A retrospective, descriptive, cohort study was conducted. Patients who had chest RT and underwent ESE with Treadmill Bruce Stress Protocol, from 2000 to 2012, at Mayo Clinic Rochester and Mayo Clinic Health System were included. A univariate analysis was performed to characterize the population. An analysis including Kruskal Wallis and Pearson Chi-Squared tests was completed to identify variables associated with + SE (Table 1). Multivariable Cox Model for MACE was conducted and is shown in Table 2. A time-to-event curve using Kaplan-Meier estimates is shown in Figure 1.

Results:
We identified 113 patients, with a mean age of 67 years and a median follow-up of 15.1 years. Of those, 99% were female, 98% were breast cancer survivors, 59% had HTN, 14% DM, 11% AFib, 2% COPD, and 12% had a history of MI. All the patients received >3000cGy of Photon RT, and 57% were treated with systemic cancer therapies. A +ESE was seen in 20.3% of the patients with no significant difference in METS achieved compared with patients who had a -ESE. COPD, RT dose, and systemic therapies, specifically doxorubicin, were associated with a +ESE. The cumulative incidence of MACE was higher in the group of +ESE (p=0.029). After adjustment for HTN, DM, smoking history, hyperlipidemia, and prior MI, the HR for MACE associated with a +ESE was 1.97 (1.09-3.59).

Conclusion:
MACE was more frequent in patients with a +ESE who received chest RT and doxorubicin versus -ESE. These results support the usefulness of ESE in cancer survivors after RT as a cardiovascular screening tool.
Abstract 12968: Survival of a Left Ventricular Free Wall Rupture in a 52-Year-Old Female
Authors: Stancic Christopher , Meece Lydia , Gilbert Danielle , hamilton russell
Published: June 2023

Introduction:
Ventricular free wall rupture is an often fatal STEMI complication that has become increasingly rare thanks to early treatment of STEMI with primary percutaneous coronary intervention. Mortality is extremely high, with survival being dependent on early diagnosis and intervention as demonstrated in our case.

Case:
A 52 year old female with multi-vessel CAD and current tobacco use presented for acute, severe chest pain radiating to the jaw, throat, and upper back. She had been discharged the day prior after being medically managed for an inferior STEMI that had poor distal targets for CABG. Chest pain had been improving at time of discharge, but acutely worsened again the day of presentation and was accompanied by dyspnea. BP was persistently hypotensive despite aggressive fluid resuscitation. Physical exam was notable for diffuse tenderness of chest wall. Patient was alert and oriented. Troponin was down-trending from initial inferior infarct but still elevated. EKG still showed inferior infarct with no new changes. CTA chest, abdomen, and pelvis demonstrated hemopericardium and a linear focus of contrast enhancement involving the inferior left ventricular wall was seen on post-contrast images as shown in Figure 1. Patient was emergently taken to OR where intraoperative TEE with color doppler demonstrated color flow across the mid inferolateral wall consistent with myocardial perforation as seen in Figure 2. The hemopericardium was evacuated, a single-vessel coronary artery bypass-SVG to RPL was performed, and the myocardial rupture was closed with a pericardial patch. Patient survived and remained in the ICU for 10 days before being discharged.
Abstract 12999: Persistent Left Superior Vena Cava Draining Directly Into Left Atrium With Occluded Coronary Sinus: A Rare Incidental Finding
Authors: Hana David , Miller Tyler C , Kadiyala Madhavi , Schwartzman David , Mascio Christopher , Hamirani Yasmin
Published: June 2023

Case presentation:
A 43-year-old lady with pacing induced cardiomyopathy presented for pacemaker (PM) revision to biventricular PM. Medical history included complete heart block with dual-chamber PM, supraventricular tachycardia, and ventricular septal defect repair. During the procedure, numerous unsuccessful attempts were made to access the right atrium (RA) using a deflectable catheter through the left subclavian vein. Left upper extremity venography exhibited a persistent left superior vena cava (PLSVC) suspected to be entering RA through the coronary sinus (CS). Navigation of the CS was unsuccessful. As a result, the procedure was aborted, and the patient was admitted for further cardiac imaging evaluation. Transesophageal echocardiography demonstrated an abnormal blood vessel between left atrial appendage and left upper pulmonary vein. Findings confirmed with agitated saline injection into left arm. This rang a concern for unroofed coronary sinus. Surprisingly, cardiac computed tomography angiograms and left upper extremity venogram images revealed a PLSVC draining into left atrium (LA) posteriorly. Normal anatomy of the right-sided superior vena cava (RSVC). Also, a CS atresia and coronary venous drainage to LA inferiorly.

Discussion:
PLSVC is a rare cardiac anomaly with estimated prevalence of 0.2% - 3% among general population. Commonly PLSVC drains into RA through expanded CS and rarely into LA through unroofed CS. Uniquely like our patient, the PLSVC drains directly into the LA with atretic CS and no interatrial communication. PLSVC is usually asymptomatic and detected incidentally during invasive cardiac procedures. Despite existence of right to left shunt, patient was maintaining normal oxygen saturation even after a treadmill stress test. Crowdedness of the RSVC with previously implanted leads is likely the reason for failed passage of the catheter to RA. Cardiac arrhythmias and paradoxical embolization were reported with PLSVC.
Abstract 13011: A Rare Case of Spontaneous Coronary Artery Dissection
Authors: Zbarsky Dmitri , sternberg evan , Diniotis Bobby , Ibrahim Zeina , Kovacs Daniela
Published: June 2023

Introduction:
Spontaneous coronary artery dissection (SCAD) is a rare condition; an intimal tear or bleeding of vasa vasorum leads to the creation of a false lumen filled with intramural hematoma. The hematoma causes coronary stenosis, leading to subsequent myocardial ischemia. SCAD is the cause of Acute Coronary Syndrome (ACS) in 0.1 to 4% of cases. Men account for less than 10% of cases, with a mean age of 48.6.

Case Study:
A 19-year-old male with prior medical history of morbid obesity and marijuana use was transferred from another hospital to our service after presenting with non-ST elevation MI. He was admitted following 30 minutes of a throbbing/pressure-like sensation in his throat, one episode of vomiting, and paresthesia in his left arm that spontaneously resolved. Initial EKG showed sinus rhythm with early repolarization changes. His troponin rose from 0.2 to 18 ng/mL. Upon admission, his high sensitivity troponin peaked at 15,000 pg/mL. Repeat EKG showed dynamic changes with T wave inversions in the inferolateral leads. The patient underwent an angiogram showing a diffuse, mid-LAD 40% de novo spontaneous dissection and a diffuse, distal-LAD 20% de novo spontaneous dissection with TIMI grade 3 and 2 flow, respectively. A repeat angiogram two days later showed improved coronary artery flow and deemed a low-risk lesion with stable patient hemodynamics; no intervention followed. The patient was treated conservatively with DAPT and discharged home with an outpatient Cardiology follow-up. A plan to have further imaging in 4 weeks to assess hematoma resolution was made.

Conclusions:
This case demonstrates an atypical presentation of SCAD in a very low-risk patient, given his sex, age, and clinical presentation of nonspecific chest pain. This case highlights the importance of high clinical suspicion for SCAD regardless of ACS risk profile in a patient presenting with chest pain.
Abstract 13016: Tumor or Thrombus?: Intracardiac Thrombus Masquerading as a Tumor
Authors: Mahesh Ashwin , Kumar Manish , Meng Joyce
Published: June 2023

Introduction:
Intracardiac masses comprise thrombi, vegetations, and tumors. Multimodality imaging modalities are often relied upon for a definitive diagnosis. We present a case of a left ventricular (LV) thrombus with characteristic of on contrast echocardiography that thrombus based on cardiac MRI. The mass resolved with anticoagulation.

Case:
A 56-year-old male with non-ischemic cardiomyopathy was admitted for management of decompensated heart failure. Transthoracic echocardiography (TTE) showed reduced left ventricular ejection fraction of 20 to 25% with diffuse hypokinesis. There was a newly detected large intracardiac mass seen in the left ventricle (figures 1-3) that enhanced with echocardiographic contrast (figure 2). Delay enhancement imaging on cardiac MRI, however, revealed a hypodense mass suggestive of a thrombus (figure 3). The patient started anticoagulation. An echocardiogram performed a month later revealed complete resolution of mass, confirming the thrombotic nature of mass (figure).

Discussion:
Contrast enhancement echocardiography is very helpful for characterization of intra-cardiac masses. Tumors usually enhance with contrast while thrombi are generally dark. Our case is unusual, the cardiac mass hyper-enhanced with echocardiographic contrast but had thrombus-like characteristics on cardiac MRI. The mass was proven to be a thrombus over time since it resolved with anticoagulation. Echocardiographic contrast usually fails to penetrate hard, chronic thrombi. However loosely structured, fresh thrombi may allow some passage of contrast. This has been demonstrated in carefully conducted in-vitro studies showing that imaging characteristics of newly formed thrombus is often bright with echocardiographic contrast. This underscores the importance of multi-modality imaging to diagnose the nature of a cardiac mass.
Abstract 13034: Reduction in Cardiovascular Disease Mortality Rates in Brazil is Heterogeneous Across Municipalities: Estimates From the Global Burden of Disease Study, 2000-2018
Authors: Brant Luisa C , Souza Juliana B , Nascimento Bruno R , Ribeiro Antonio L , Malta Deborah C
Published: June 2023

Introduction:
Age-standardized mortality rates (ASMR) for cardiovascular diseases (CVD) decreased in Brazil in the last decades due to better control of risk factors and access to treatment. However, how this reduction distributes across the country’s municipalities is not known, which is important due to the socioeconomic and healthcare disparities in its regions (Northern regions being the most vulnerable) and in municipalities with small vs. large populations.

Methods:
Ecological study in which the ASMR for CVD were estimated by the Global Burden of Disease (GBD) method for 5,568 Brazilian municipalities from the 5 regions in the triennials: 2000-2002, 2009-2011, and 2016-2018. A visuospatial analysis was applied to create clusters in ASMR with Moran Local analysis. Municipalities were then stratified by population size in <30,000, 30,000-300,000, and >300,000 inhabitants per region, and the % changes in ASMR from 2000-2002 to 2016-2018 were calculated.

Results:
In 2000-2002, ASMR for CVD were higher in the more developed regions and in the larger municipalities of all regions, except the South. In 2016-2018, CVD ASMR became higher in the least developed Northern regions (
Fig 1
). Moreover the % reduction in CVD ASMR were lower in small vs. large municipalities within all 5 regions varying from -7% in the small North municipalities to -78% in the large South municipalities.

Conclusions:
Reduction in CVD mortality in Brazil was lower in the municipalities from the most vulnerable regions and in those with smaller populations. Public policies focusing and tailored to these smaller municipalities, particularly of the least developed regions must be considered a priority.
Abstract 13045: Increased Recognition of Transthyretin Amyloid Cardiomyopathy as a Cause of Heart Failure in Women
Authors: Prasad Mark , Kim Morris , Chandrashekar Pranav , Zhao Yuanzi , Fischer Katherine , Nazer Babak , Masri Ahmad
Published: June 2023

Introduction:
Recognition of transthyretin amyloid cardiomyopathy (ATTR-CM) as a cause of heart failure has increased over the past decade. ATTR-CM, particularly wild type (wtATTR-CM), is considered to mainly affect men. Tafamidis was approved by the FDA for the treatment of ATTR-CM based on the results of the ATTR-ACT trial, which only included 13 women with wtATTR-CM (out of 335). We investigated the proportion of women diagnosed with ATTR-CM over time and compared their presenting characteristics to men.

Hypothesis:
Improved recognition of ATTR-CM has uncovered a higher prevalence of ATTR-CM in women compared to historical estimates.

Methods:
We compared the presenting characteristics of women to men diagnosed with ATTR-CM. We also compared the proportions of women with ATTR-CM diagnosed before 2019 with those diagnosed 2019-2022. Subgroup analysis of wtATTR-CM patients was performed as well.

Results:
Over the study period, 140 consecutive patients (81% wild type, 11.4% women) with ATTR-CM were included. The rate of diagnosis of hereditary ATTR-CM in women did not change from pre 2019 (4/69 or 6%) to 2019-2022 (5/71 or 7%). However, for wtATTR-CM, there were 0 women and 51 men diagnosed prior to 2019 as compared to 7 women (11%) and 62 men from 2019-2022. There were several differences in the presenting characteristics between men and women in the combined ATTR-CM group (Table). However, in the wtATTR-CM group, the only significant differences were higher left ventricular ejection fraction and smaller systolic and diastolic diameters in women (Table).

Conclusions:
There has been a rapid increase in the rate of diagnosis of wtATTR-CM in women. Ongoing education and a changing diagnostic landscape will redefine wtATTR-CM epidemiology.
Abstract 13079: Reduced Apoj-Glyc Serum Levels Identify Patients With Cardiac Ischemic Events Among Those Attending the Emergency Department With Chest Pain
Authors: Kaski Juan-Carlos C , Cubedo Judit , Lluch Nuria , Lopez-sendon Jose L , Gorog Diana , Antorrena Isabel , Avanzas Pablo , Herrero Puente Pablo , Sionis Alessandro , Gonzalez-Juanatey Jose R , Iñiguez Andrés , Cordero Alberto , Ako Emmanuel , Fernandez-Aviles Francisco , Atienza Felipe , Recio-Mayoral Alejandro , Badimon Lina
Published: June 2023

Introduction:
Glycosylated apolipoprotein J (ApoJ-Glyc) has been suggested to be a marker for the early detection of myocardial ischemia. Ischemia induces an intracellular accumulation of non-glycosylated ApoJ that mirrors a reduction in ApoJ-Glyc serum concentration in acute ischemic syndromes.

Objective:
The EDICA clinical trial - multi-centre, international, diagnostic study (NCT04119882)- was carried out to assess the performance of ApoJ-Glyc as a biomarker for the early detection of myocardial ischemia in patients attending the A&E department with chest pain suggestive of acute coronary syndrome (ACS).

Methods:
EDICA assessed 404 patients. Blood samples were obtained on admission, for assessment of high sensitivity-troponin (hs-Tn) and ApoJ-Glyc. ApoJ-Glyc serum levels were analyzed with a novel ELISA, targeting a specific glycosylated variant of ApoJ (ApoJ-GlycA6).

Results:
Based on clinical diagnostic tests, 291 patients were given a final diagnosis of “non-ischemic” event and 113 patients were considered to have had an ischemic event (33 STEMI, 48 NSTEMI, 27 Unstable Angina and 5 “unclassifiable” ACS). ApoJ-GlycA6 levels were significantly lower on admission in ischemic patients, compared with non-ischemic patients (66 [46-90]
vs.
73 [56-95] μg/ml, respectively; P=0.04). Ischemic patients who underwent PCI and had a pre-PCI TIMI 0-2 flow showed significantly lower ApoJ-GlycA6 levels at admission compared with non-ischemic patients (64 [37-81]
vs.
73 [56-95] μg/ml; P=0.01). Of interest, 51% of ischemic patients, had “inconclusive” or negative hs-Tn at admission. Among these, ApoJ-GlycA6 identified the ischemic event in 48% (<66 μg/ml).

Conclusions:
ApoJ-Glyc concentration decreased in patients with documented myocardial ischemia, compared with patients with a final diagnosis of “non-ischaemic” event. Patients with reduced TIMI flow indicative of poorer myocardial perfusion were among those with the lowest ApoJ-Glyc concentration. ApoJ-Glyc was low in ischemic patients irrespective of hs-Tn concentration. The results confirm the potential role of ApoJ-Glyc as a biomarker for the early detection of cardiac ischemia that could provide complementary information to that afforded by current biomarkers and diagnostic tests.
Abstract 13086: Mid-Term Feasibility of Left Bundle Branch Area Pacing With Standard Stylet-Driven Pacing Leads and Predictors of Success: A Multicenter Center Experience
Authors: Gain Yu , Kim Tae-Hoon , Yu Hee Tae , JOUNG BOYOUNG , Pak Hui-Nam , LEE Moon Hyoung
Published: June 2023

Introduction:
Conventional right ventricular apical pacing can cause electrical-mechanical dyssynchrony. For this reason, physiological pacing was considered and became the background for the development of his bundle pacing (HBP). Recently, left bundle branch area pacing (LBBAP), which overcomes the shortcomings of HBP, has been implemented.

Hypothesis:
Initially, LBBAP was achieved through a lumen-less lead, and it has been reported that LBBAP using a standard stylet-driven lead (SDL) is also available. The purpose of this study is to establish the feasibility and mid-term outcome of LBBAP using SDL, and to investigate the predictors of success.

Methods:
This study enrolled a total of 119 patients who underwent LBBAP from December 2020 to February 2022. LBBAP was performed with a 5.6Fr stylet-driven pacing lead with an extendable helix (Solia S60, Biotronik, SE & Co, KG). We analyzed the initial outcomes of the procedure, including the success rate and complications, and identified predictive factors that affect them. lead parameters were assessed in follow up.

Results:
Total success rate of lead implantation of LBBAP with conventional stylet-driven lead was 95.8% for entire period and showed increase in success rate as the number of procedures increased. In the multivariate analysis, The larger the RA size, the greater the number of trials (Estimates = 1.770 [1.10 - 2.44], p = <0.001) and the smaller the RV size, the greater the number of trials (Estimates = -0.923 [-1.64 - -0.21], p = 0.012). The mean thresholds at implant, 2 months, 6 months were 0.90 ± 0.80 V at 0.5 ms, 0.80 ± 0.16 V at 0.5 ms, and 0.87 ± 0.28 V at 0.5 ms respectively in total period.

Conclusions:
LBBAP with conventional stylet-driven lead is a feasible and safe pacing modality. It has a high success rate and fewer complications, satisfied and stable lead parameters in intermediate-term observations.
Abstract 13094: Extracellular Vesicles Associate With Cardio-Metabolic Status and Endothelial Dysfunction in a Cohort of African-American Women
Authors: Miller Noel , Baumer Yvonne , Bavuso Matthew , Colunga Biancatelli Ruben Manuel Luciano , Mitchell Valerie , Collins Billy , Powell-Wiley Tiffany , Dobrian Anca
Published: June 2023

Extracellular vesicles (EVs) are emerging as promising biomarkers for cardiovascular disease (CVD) and contributors to CVD pathogenesis. Plasma EVs access the endothelium from various vascular beds allowing them to impact endothelial function and inform on the global particulate secretome produced by parenchymal, vascular and immune cells. In this study we examined associations between plasma EVs and biochemical and physiological parameters in a cohort of African American (AA) women at risk for CVD. We also examined EV effect on coronary endothelial function. This study will serve as baseline data for a longitudinal study aimed to determine the effects of exercise on EVs and endothelial function in a similar cohort.A cohort of 24 AA women between 22-71 yrs, with BMI between 26-47 kg/m
2
and ASCVD risk scores between 2.3-22.1 were included in the study. EVs were isolated from fasted heparinized plasma using size exclusion chromatography. EV size and numbers were determined using nanoparticle tracking analysis. Lipids, inflammatory cytokines, and metabolic panels were measured at the time of blood draw. Human coronary endothelial cells were treated with EVs from participants and endothelial barrier function and migration were measured using ECIS technology. Associations were determined using multivariable linear regression analysis, adjusted for BMI and ASCVD risk.We found a negative association (beta=-0.712, p<0.01) between total triglycerides (TG), TG rich lipoprotein (Lp), and EV size; EV concentration was positively associated (beta= 0.51-0.61, p<0.01) with TG rich Lp, LDL cholesterol and TNFa. Reduced endothelial barrier function due to EVs was positively associated with monocyte counts (beta=0.42, p<0.05). EVs effect on increased endothelial migration was strongly and negatively associated with monocyte counts (beta=-0.85, p<0.001), IL8 and CXCl10 (beta=-0.56-0.46, p<0.05).Collectively these data show that EVs number and size strongly associate with circulating lipids, while EV impact on endothelial dysfunction is associated with inflammatory markers. EVs are therefore promising indicators of endothelial dysfunction that associate with inflammatory and metabolic markers even after adjusting for BMI and ASCVD risk.
Abstract 13096: Outcomes After Coronary Artery Bypass Grafting With Bilateral Internal Mammary Arteries in Obese Patients
Authors: Nakai Chikashi , Zhang Cheng , Cohen Jeffrey , Shults Christian , Waksman Ron , Molina Ezequiel J
Published: June 2023

Introduction:
The purpose of this study was to evaluate the postoperative outcomes with the use of bilateral internal mammary artery (BIMA) conduits in obese patients.

Methods:
Between January 2003 and December 2018, 8109 patients underwent isolated coronary artery bypass grafting (CABG) at our institution, including 7218 (89.0%) treated with single internal mammary artery (SIMA) and 891 (11.0%) treated with BIMA. Patients were divided into three groups according to preoperative body mass index (BMI), normal or BMI<25 (22.2%), overweight or 25-BMI<30 (37.2%), and obese or BMI>30 (40.6%). In each group, BIMA and SIMA patients were compared to investigate the thirty-day mortality and postoperative complications. Significant baseline differences were observed between the three BMI groups and such differences were adjusted via inverse probability weighting matching.

Results:
The thirty-day mortality, deep sternal wound infection (DSWI) rates and length of hospital stay were 1.4%, 0.5%, and 6.0 ± 9.1 days for the normal group, 0.2%, 1.0% and 5.5 ± 4.2 days for overweight group and 0.9%, 1.8% and 5.5 ± 4.0 days for the obese group. There was no significant difference in the thirty-day mortality, incidence of DSWI and hospital stay between BIMA and SIMA groups, except in the obese group where the rate of DSWI was significantly higher in the BIMA patients (3.4 vs 0.0%, p=0.02).

Conclusions:
BIMA for isolated CABG in obese patients can be used without an increase of the thirty-day mortality and hospital stay. However, the use of BIMA in obese patients may lead to an increase of postoperative DSWI.
Abstract 13115: Impact of Socioeconomic Status and Remoteness of Residence on Access to Cardiac Care for Pediatric Heart Disease in Alberta, a Jurisdiction of Universal and Centralized Cardiac Healthcare
Authors: Hornberger Lisa K , Smith Christopher , Dover Doug C , Mackie Andrew S , Kaul Padma , Conway Jennifer
Published: June 2023

Introduction:
Socioeconomic status (SES) and remoteness of residence (RoR) impact access to care and outcomes in congenital (CHD) and acquired (AHD) pediatric heart disease. Whether the universal, centralized Canadian healthcare system mitigates such inequities is unclear. We examined associations between SES and RoR on age at cardiac diagnosis (ACD), time to first intervention (TFI), and annual primary care (PCV) and cardiology (CV) visits as evidence of healthcare access in Alberta.

Methods:
All children born and diagnosed in Alberta with CHD or AHD from 2005-2017 were included. CHD was classified as mild, moderate, and severe base on the Bethesda Task Force definitions. Geospatial modelling was used to determine drive times (<60, 60-180, >180 minutes) to 1 of 2 provincial cardiac programs. Cox proportional hazards regression models were used to examine relationships between RoR and SES with ACD and TFI, and Poisson models using generalized estimating equations for annual PCV and CV.

Results:
Of 12,542 children, 9347 had mild, 1733 moderate and 717 severe CHD and 745 AHD. Most (8,833, 70.4%) lived <60 minutes to a cardiac center, and the largest proportion were in SES quintile 1 (least vulnerable, 3,074, 24.5%) and smallest in quintile 5 (most vulnerable, 2003, 16.0%). Median ACD was 1(IQR 0-108) days for mild, 0(0-54) days for moderate, and 0(0-0) days for severe CHD, and 340(41-1312) days for AHD. Intervention occurred in 1086(62.7%) with moderate CHD (TFI 63(7-150) days), 588(82.0%) with severe CHD (11(5-58) days), and 42 with AHD (1828(793-2866) days). ACD was impacted slightly by SES and only in AHD (Table). TFI and PCVs were not impacted by RoR or SES. Finally, CVs were inversely related to RoR for CHD and AHD.

Conclusions:
In Alberta, SES and RoR do not importantly impact ACD, TFI and PCVs among CHD and AHD patients. Greater RoR but not SES, however, is associated with fewer annual CVs, suggesting a need to optimize cardiac outreach services.
Abstract 13117: Gender Parity in High Impact Cardiology Journals
Authors: Petrechko Oksana , Faturos Andrew , Khan Umair A , Sagheer Shazib , Pal Suman , Shekhar Rahul , Barrett Eileen , Sheikh Abu Baker B
Published: June 2023

Background:
Despite advances in representation of women in medical training, women continue to be underrepresented in cardiology, particularly in senior roles of authorship and leadership. Analyzing trends in high-impact cardiology journals can highlight underrepresentation of women and help elucidate barriers to female representation in academic cardiology.

Methods and Results:
Using the SCImago Journal and Country Rank (SCR), we analyzed 20 journals (31,540 total articles) in cardiology and cardiovascular medicine with the highest total citations from January 1
st
2018 to October 31
st
2021 for gender distribution of editorial staff and authorship. Gender of individuals was classified using biographical information from public and personal media sources. In cases of ambiguity, Genderize.io was used to help predict gender at probability of ≥95%. Our data demonstrated that 27% of articles had women as first authors and 20% as senior authors. Men constituted the majority of both first authors (73%) and senior authors (80%). The editorial staff was 77% men, with women accounting for 23%. Only 10% of editors-in-chief were women. There was a statistically significant negative correlation between the percentage of women first authors and percentage of men on the editorial board. There was no statistical significance between journal impact factor and percentage of men and women as authors. Overall, female authorship increased from 26% first and 19% senior authors in 2018 to 29% first and 22% senior authors in 2021.

Conclusion:
Women are significantly under-represented in the field of cardiology as first or senior authors, editorial board members, and editors-in-chief in the top medical journals. Although there has been a slight uptrend in percentage of women occupying leading publishing roles, parity with men is still a work in progress. Additional work is needed to identify and address barriers to publishing and academic advancement for women physicians in cardiology.
Abstract 13125: Endotrophin as a Marker of Outcomes in Heart Failure With Preserved Ejection Fraction Patients With and Without Diabetes
Authors: Moeller Alexandra L. , Reese-Petersen Alexander , Palau Patricia , Dominguez Eloy , Karsdal Morten , Genovese Federica , Nuez Llota Julio E
Published: June 2023

Introduction:
Hyperglycemia-mediated tissue injury can lead to cardiac fibrosis and vascular damage, key drivers of heart failure with preserved ejection fraction (HFpEF). We investigated the potential of endotrophin (ETP), a pro-fibrotic molecule generated during type VI collagen formation, as a risk marker of outcomes in HFpEF patients with and without diabetes from the TRAINING-HF study.

Methods:
We measured ETP by the PRO-C6 ELISA in serum from 48 patients with symptomatic HFpEF (42% males, mean±SD age of 73±9 years, 45% with diabetes). Outcomes included hospitalization for heart failure (HHF) and all-cause mortality. Cox proportional hazards models adjusted for conventional risk factors (age, sex, BMI, systolic blood pressure, and smoking), and ROC curve- and Kaplan-Meier analyses adjusted for diabetes (multiple logistic regression) were applied.

Results:
Levels of ETP were significantly elevated in patients experiencing HHF (p=0.009), all-cause mortality (p=0.034), and underlying diabetes (p=0.018). Higher levels of ETP were independently associated with HHF (hazard ratio (HR): 2.29, p=0.002) and all-cause mortality (HR: 2.1, p=0.002) when adjusted for conventional risk factors. There was no interaction between ETP and the presence of diabetes (p=0.97; p=0.08, respectively). In crude analyses, levels of ETP were significantly associated with the risk of HHF and all-cause mortality (AUC=0.75, p=0.004; AUC=0.79, p=0.004, respectively) and a significantly increased risk of HHF (p=0.01) and all-cause mortality (p=0.006) was seen with increasing tertiles of ETP. When adjusting for diabetes, the prognostic potential of ETP for HHF and all-cause mortality remained significant (AUC=0.76, p=0.007; AUC=0.77, p=0.008, respectively), and there was a significant association between increasing tertiles of ETP and HHF (p=0.018), but not for all-cause mortality (p=0.112).

Conclusions:
Levels of ETP were significantly elevated in HFpEF patients with diabetes. Interestingly, ETP was independently associated with the risk of HHF and all-cause mortality when adjusting for diabetes. Further studies are needed to investigate how diabetes impacts the prognostic potential of ETP in HFpEF patients.
Abstract 13131: Three-Dimensional Echocardiography Left Atrial Appendage Dimensions is a Reflect of Cardiac Rhythm at Mid-Term Follow-Up in Atrial Fibrillation Patients
Authors: Soulat-Dufour Laurie , SIMON Theo , Lang Sylvie , EDERHY Stephane , ADAVANE Saroumadi , Chauvet-Droit Marion , Nhan Pascal , Capderou Elodie , Kamami Iris , Arnaud Camille , Lebos Pierre-Antoine , Issaurat Pauline , Boccara Franck , Cohen Ariel
Published: June 2023

Introduction:
Few studies have described the characteristics of the left atrial appendage (LAA) using three dimensional (3D) transesophageal echocardiography (TEE) in atrial fibrillation (AF).

Hypothesis:
We hypothesized that 3D characteristics of the LAA could further characterize patients in AF.

Methods:
We prospectively evaluated 156 patients hospitalized for AF with two-dimensional (2D) transthoracic and 3D TEE of the LAA within 24 hours of admission. 3D parameters were off-line analysed with Tomtec software (4D Cardio-View, Generic Volume, Philips) (Figure 1A). Patients were divided into two groups according to the cardiac rhythm at 2 years of follow up: restoration of sinus rhythm (SR group, 107 patients) or persistence of atrial fibrillation (AF group, 49 patients).

Results:
The mean age of the population was 66±11 years and 95 (61%) patients were male. At admission using 2D transthoracic echocardiography, AF group had in comparison with SR group higher left atrial end-systolic volume indexed (respectively 48.0 (38.7-57.0) versus 41.8 (35.0-51.5) ml/m
2
, p=0.0096), higher E velocity (respectively 0.90 (0.78-1.00) versus 0.76 (0.62-0.91) m/s, p= 0.0001) and higher pulmonary arterial pressure (respectively 31 (25-38) versus 28 (23-33) mmHg, p=0.0142). There were no significant differences in left ventricle ejection fraction and right atrial end-systolic volume indexed. At admission using 2D TEE, AF group had in comparison with SR group lower emptying flow velocity (29 (20-38) versus 38 (26-53) cm/s, p=0.002) and filling flow velocity (29 (20-39) versus 40 (29-56) cm/s, p=0.001) of the LAA. In 3D TEE, AF group had higher 3D end-systolic and end-diastolic LAA volumes (non-indexed and indexed) and no significant differences in LAA ostium in comparison with SR group (Figure 1B).

Conclusions:
3D evaluation of the LAA reflects a degree of cardiac cavities remodeling in AF and seems to be associated with the evolution of cardiac rhythm at two-years follow-up.
Abstract 13132: Uncontrolled Diabetes is Associated With Adverse Cardiovascular Disease Outcomes in Those With Stage B Heart Failure
Authors: Lee Emmanuel P , Ndumele Chiadi E , Zhang Sui , Matsushita Kuni , Skali Hicham , Shah Amil M , Selvin Elizabeth , Echouffo Tcheugui Justin B
Published: June 2023

Background:
Among persons with stage B heart failure (HF) (subclinical cardiac dysfunction), diabetes is associated with markedly increased risk of progression to clinical HF. Whether stage B HF indicates greater risk for other cardiovascular disease (CVD) outcomes in the presence of diabetes is unknown.

Methods:
We included ARIC Visit 5 (2011-13) participants without clinical HF who met criteria for stage A (HF risk factors) or stage B (subclinical cardiac dysfunction by echocardiogram or elevated cardiac biomarkers) HF. Across HF stages A and B, we calculated incidence rates and their differences and used Cox models to estimate hazard ratios for overall mortality, CVD mortality, coronary heart disease (CHD), and HF associated with controlled diabetes (HbA1c <7%) and uncontrolled diabetes (HbA1c ≥ 7%), compared to no diabetes.

Results:
4,774 participants (mean age 75.4, 58.3% women, 20.2% black) were followed for a median 7.3 years, with 867 deaths, 237 CVD deaths, 228 CHD events, and 470 HF events. There were significant additive interactions (increased absolute risk) associated with uncontrolled diabetes (vs. no diabetes) for total mortality, CVD death, CHD, and HF for stage B, but not stage A (Table). The incidence rate differences (per 1000 person-years) associated with uncontrolled diabetes (vs. no diabetes) were greater in stage B vs stage A for all outcomes (Table). In multivariable adjusted models, uncontrolled diabetes (vs. no diabetes) was associated with statistically significant hazard ratios (increased relative risk) for all CVD outcomes in stage B, but did not have significant associations with any CVD outcomes in stage A (Table).

Conclusion:
In stage B HF, diabetes is associated with global CVD risk. Intensive preventive efforts to avert various forms of CVD may be indicated for those with diabetes and subclinical cardiac dysfunction.
Abstract 13135: Mir455 Targets the Repeated Domains of
Lpa
Open Reading Frame and Lowers Its Expression and The Secretion of Apolipoprotein (a) From Human Cells
Authors: Chemello Kevin , Lambert Gilles
Published: June 2023

Introduction:
Lipoprotein (a) [Lp(a)] is a peculiar lipoprotein species containing a unique glycoprotein apolipoprotein(a) [apo(a)] encoded by the
LPA
gene. Lp(a) is causatively, independently and significantly associated with CAD and calcified aortic valve stenosis. MiRs are approximately 22 nucleotides in length and work by inducing RNA silencing, thus reducing target genes expression. The influence of these regulatory elements on the expression of
LPA
remains unknown.

Hypothesis:
Apo(a) and Lp(a) plasma levels are genetically regulated by miRs.

Method:
A prediction software was used to identify miR candidates targeting the human
LPA
mRNA open reading frame (ORF). We investigated the selected candidates by transfecting these miRs (i) in HEK293 cells stably expressing a short
LPA
isoform (i.e. 17 KIV domains) and (ii) in the Hep3B human hepatoma cell line that endogenously express
LPA
. A validated siRNA targeting
LPA
and a scrambled siRNA were used as positive and negative controls, respectively.
LPA
expression was assessed by RT-qPCR. Apo(a) protein expression and secretion in the culture medium were assessed by Western Blot and ELISA, respectively.

Results:
We identified four miR candidates (miR22, miR194, miR218, and miR455) based on sequence complementarity between their seed region and the
LPA
mRNA ORF. Compared with the negative control, only miR455 significantly reduced
LPA
mRNA expression (-67±8%) as well as apo(a) intracellular abundance (-41±9%) and apo(a) secretion (-36±9%) in the culture medium (
p<0.001
, all). Similar reductions were observed with the positive siRNA control (-77±4%, -41±11%, -53±11 %,
p<0.001
all, respectively). No significant effect on
LPA
expression was seen with the three other miR candidates.

Conclusion:
These
in vitro
results suggest that at least one human miR has the potential to regulate the circulating levels of Lp(a)
in vivo
. This will be verified by measuring miR455 abundance in liver and plasma samples from individuals with high vs. low Lp(a) plasma concentrations. Our study also underlines that targeting
LPA
with interfering RNAs is likely a regulatory process occurring in humans.
Abstract 13141: Age of Onset and Clinical Outcomes in
RBM20
-Mediated Arrhythmogenic Dilated Cardiomyopathy
Authors: Garmany Ramin , Tseng Andrew S , Pereira Naveen L , MacIntyre Ciorsti , Schneider Jay W , Ackerman Michael J , Giudicessi John
Published: June 2023

Introduction:
Pathogenic loss-of-function variants in the
RBM20
-encoded RNA-binding motif 20 splicing regulator cause a severe form of arrhythmogenic dilated cardiomyopathy (DCM). Erroneous splicing of
TTN
-encoded titin contributes to the pathogenesis of
RBM20
-mediated disease. However, studies exploring the clinical course of
RBM20
-mediated arrhythmogenic DCM alone or in comparison to
TTN
-mediated DCM, the most common familial cause of DCM, are lacking.

Methods:
The Mayo Clinic Genetic Arrhythmogenic Cardiomyopathy Registry (n=391) was used to identify all patients with a pathogenic/likely pathogenic (P/LP) variant in either
RBM20
or
TTN
. For the purposes of this study, a ventricular arrhythmia (VA) event was defined as sudden cardiac arrest, sustained ventricular arrhythmia, or an appropriate ICD shock and an advanced heart failure (AHF) event was defined as ventricular assist device implantation or heart transplantation.

Results:
Overall, 40 patients with a P/LP variant in
RBM20
(50% female) and 70 patients with a P/LP variant in
TTN
(43% female) were identified. The prevalence of a cardiac phenotype in patients with
RBM20-
and
TTN
-mediated disease was 88% and 83%, respectively.
RBM20
patients were more likely to have a family history of sudden cardiac arrest (78% vs 34%; p < 0.0001) and cardiomyopathy (90% vs 61%; p=0.001). No difference in rate of ICD implantation (35% versus 33%) was observed. Interestingly, the prevalence of AHF events (10% vs 6%; p=0.5) and VA events (28% vs 24%; p=0.7) was similar between
RBM20
- and
TTN
-positive patients. However,
RBM20
patients were younger than
TTN
patients at the time of their event (37 ± 18 years vs 50 ± 17; p=0.0004). Time-to-event analysis showed
RBM20
patients had an earlier time to AHF event (p=0.05) and time to VA event (p=0.03) than
TTN
patients. The mean age for AHF events was 25 years for
RBM20
patients (N=4) and 47 years for
TTN
patients (N=4). The mean age for VA events was 29 years for RBM20 patients (N=10) and 42 years for
TTN
patients (N=14).

Conclusions:
RBM20
-mediated arrhythmogenic DCM represents a highly penetrant genetic heart disease with potentially life-threatening VAs and end stage heart failure manifestations occurring at a significantly younger age in comparison to
TTN
-mediated DCM.