bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12728: The Addition of Social Determinants of Health Improves the Predictive Accuracy of the Pooled Cohort Equations for 10-year Ascvd Events in African Americans
Authors: Hammond J G , Waken RJ , Sims Mario , Henderson Kamal , Joynt Maddox Karen E
Published: June 2023

Introduction:
The gold standard risk prediction tool for atherosclerotic cardiovascular disease (ASCVD), the Pooled Cohort Equations (PCE) underestimates risk among the socially disadvantaged, yet social determinants of health are absent from the PCE. This may be contributing to racial inequities in CVD since due to systemic and structural racism, socioeconomic disadvantage is disproportionately concentrated in African American (AA) communities. This analysis aimed to determine whether SDOH variables were important for the prediction of 10-year ASCVD risk in a large cohort of AA and to test whether the addition of these variables improved PCE model performance.

Methods:
Retrospective observational study of 3,470 Jackson Heart Study (JHS) participants aged 40-79 years old without prior ASCVD at baseline study visit. 10-year ASCVD event was defined as stroke, MI, or death from MI. First, we used competing risk random survival forests to determine variable importance of risk factors, then we used cox-proportional hazards to identify which variables among those found to be important, were independently associated with our outcome. We used time dependent AUC to compare the performance of PCE alone to models with the PCE plus SDOH to assess concordance with the true event rates for prediction of 10-year ASCVD.

Results:
Our sample was 35% male, 100% AA and 46% of participants had an income of <$35K/year. Of 30 SDOH factors tested, the following 6: BMI, depression, weekly stress, insurance status, family income, and neighborhood violence were determined most important for prediction and were independently associated with 10-year ASCVD risk. In this sample, the PCE only model had an AUC of 0.822; adding a limited panel of SDOH factors - income, insurance status and occupation, increased the AUC to 0.859, but this improvement was only statistically significant at the 0.10 level (p=0.093). The model adding the full 6 SDOH risk panel to the PCE, saw the highest AUC at 0.863 (p=0.029).

Conclusions:
Adding SDOH risk factors to the PCE improved risk prediction. These findings should be explored in a larger database to determine if adding SDOH to the PCE can improve risk prediction for ASCVD events among vulnerable populations and guide more optimal use of prevention strategies.
Abstract 12736: Cardiac Fludeoxyglucose-18 Positron Emission Tomography in Genotype-Positive Arrhythmogenic Cardiomyopathy
Authors: Tseng Andrew S , Garmany Ramin , MacIntyre Ciorsti , McLeod Christopher J , Cooper Leslie T , Ackerman Michael J , Siontis Konstantinos , Giudicessi John
Published: June 2023

Introduction:
Myocardial inflammation likely contributes to the pathogenesis of arrhythmogenic cardiomyopathy (ACM), a clinically and genetically heterogenous disorder characterized by ventricular dysfunction and potentially life-threatening ventricular arrhythmias. Due to phenotypic overlap, some patients with genetic ACM may have been evaluated for an underlying inflammatory cardiomyopathy, namely cardiac sarcoidosis. However, the cardiac fludeoxyglucose (FDG) positron emission tomography (PET) findings in ACM patients have not been assessed systematically.

Methods:
All genotype-positive patients in the Mayo Clinic ACM registry who received a cardiac FDG PET were included in this study. The cardiac FDG PET scan consisted of a resting myocardial perfusion scan with N13-ammonia as well as a F18-FDG scan after a high-fat diet to suppress physiologic FDG uptake. Pertinent demographic, genetic, imaging, and outcome data were extracted from the medical record.

Results:
Collectively, 12 (75% female) genotype-positive ACM patients received a cardiac PET FDG scan as part of their clinical evaluation (median age at scan 45.3 years [IQR 38.9-62.1]). Amongst these patients, pathogenic/likely pathogenic variants were detected in
LMNA
(n=7),
DSP
(n=3),
FLNC
(n=1), and
PLN
(n=1). Of note, 6/12 (50%) had abnormal myocardial FDG uptake, including diffuse (entire myocardium) uptake in 2/6 (33%), focal (1-2 segments) uptake in 2/6 (33%) and patchy (3+ segments) in 2/6 (33%). Median myocardial standardized uptake value ratio was 2.1 (IQR 1.5-2.6). Interestingly,
LMNA
-positive patients accounted for 3 out of 6 (50%) positive studies (diffuse uptake in 2 and focal uptake in 1).

Conclusion:
Myocardial FDG uptake is common in genetic ACM patients undergoing cardiac FDG PET. This finding further supports the role of myocardial inflammation in genetic ACM and demonstrates the ability of cardiac FDG PET to readily detect this phenomenon. Further investigation is needed to determine (i) the role of cardiac FDG PET in the evaluation of genetic ACM, (ii) if FDG uptake in genetic ACM has prognostic value and (iii) whether the attenuation of myocardial inflammation with immunosuppressive agents can impact the clinical course of inflammatory genetic ACMs.
Abstract 12738: Tracking Fluoroscopic Time Amongst Cardiology Trainees
Authors: Leon William , Stripe Benjamin
Published: June 2023

Introduction:
ACC and ESC guidelines for cardiologists in training recommend 200-300 coronary angiographies as primary operator before completion of training. There are different ways to measure an operator's proficiency of performing a coronary angiogram including contrast volume, fluoroscopy time, and total time of procedure. Data from previous studies has shown that fluoroscopy time is the best measure of trainee progression. Fluoroscopy time is significantly longer in trainees who have performed less than 100 interventions.

Objectives:
Utilize fluoroscopy time during cardiac catheterization to help direct safety in cardiology trainees.

Methods:
Cardiac catheterization operator data from UCD cardiology fellows between 2014 - 2017. Data was categorized into 3 categories: left heart catheterizations (LHC) , right heart catheterization (RHC), and left and right catheterization combination (LHC + RHC). Data was excluded if the operator performed any other procedure in addition to catheterization. Data was analyzed using a One-way ANOVA analysis.

Results:
A total of 853 cardiac catheterizations performed by trainees. LHC fluoroscopic time declined from year 1 (9.64 mins) to year 2 (7.62 mins, p: 0.009) (figure 1). LHC + RHC fluoroscopic time declined from year 1 (12.89 mins) to year 2 (10.77 mins, p: 0.007). There was no statically significant change in fluoroscopic time in operators over their three years of training who performed RHC. Operators in their third year of training did not have any statistically significant improvement in their fluoroscopic time when compared to their second year of training.

Conclusions:
Fluoroscopic time decreases after first year of training in LHC and LHC + RHC cases. There is no significant change in fluoroscopic time amongst fellows who perform RHC regardless of years of experience. Safety efforts to minimize fluoroscopic time should be focused on fellows in their first year of training
Abstract 12757: Competing Neurotrophic and Anti-Neurotrophic Remodeling Processes in PVC-Induced Cardiomyopathy
Authors: Myadam Rahul , Wang Li , Villalobos Jaime B , Medina Contreras Juana Maria de Lourdes , Das Anindita , Kaszala Karoly , Ellenbogen Kenneth , Eltit Jose , Huizar Jose F , Tan Alex Y
Published: June 2023

Introduction:
We previously demonstrated evidence of pro-arrhythmic sympathetic hyperinnervation and hyperactivity of the stellate ganglia in Premature Ventricular Contraction-induced Cardiomyopathy (PVC-CM). However, the presence of neural remodeling within the myocardium remains unclear.

Methods:
In a canine model of PVC-CM induced by a novel premature pacing algorithm with 12-weeks of bigeminal short-coupled (200ms) PVC exposure, we performed ELISA of serial plasma norepinephrine levels at baseline vs PVC-CM (N=7), and western blotting of neural proteins and beta-adrenoreceptors using snap-frozen left ventricular free wall myocardium in 6 sham controls and 7 PVC-CM hearts.

Results:
We found increased trans-cardiac norepinephrine (NE) levels in PVC-CM vs controls (Fig. 1A), increased LV myocardial sympathetic nerve protein Tyrosine Hydroxylase (TH) (Fig.1B) but interestingly, decreased Growth Associated Protein (GAP) 43 (Fig.1C), a marker of sprouting nerve cones. There was no change in synaptophysin (SYN), a neural synapse protein, or Choline acetyltransferase (ChAT), a parasympathetic nerve marker (Fig.1D). Further downstream, we found reduced ß-1 receptor levels similar to other forms of heart failure but markedly increased ß-2 receptor levels (Fig.1E), a finding unique to PVC-CM. Functionally, ß-2 effects are known to oppose the ß-1 inotropic and pro-apoptotic effects in the human myocardium

Conclusions:
There are competing neurotrophic vs anti-neurotrophic processes occurring within the LV myocardium, along with downstream beta-receptor changes. We hypothesize that these changes are a chronic adaptive response to PVC-induced chronic sympathetic surge, that ultimately protect against sympathetic excess and its consequent downstream effects on myocardial calcium handling and inotropy. These changes may have implications for the pathogenesis of PVC-CM and its pro-arrhythmic consequences.

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Abstract 12761: Association of Androgen Deprivation Therapy With Metabolic Disease in Prostate Cancer Patients: An Updated Meta-Analysis
Authors: Swaby Justin D , Aggarwal Ankita , Batra Akshee , Jain Anubhav , Seth Lakshya , Stabellini Nickolas , Klaassen Zachary , Barata Pedro , Sayegh Nicolas , Agarwal Neeraj , Terris Martha , Guha Avirup
Published: June 2023

Introduction:
Androgen deprivation therapy (ADT), a backbone treatment for advanced prostate cancer (PC) is known to have a variety of metabolic side effects. We conducted an updated meta-analysis to quantify metabolic risks of ADT.

Hypothesis:
We hypothesized that ADT would increase the risk for metabolic diseases compared to PC patients not on ADT.

Methods:
We searched PubMed, Web of Science, and Scopus in May of 2022 for studies that investigated the risk of metabolic syndrome (MetS), diabetes, and hypertension from ADT in PC patients using keywords. 4 blinded reviewers screened studies. Only studies that had a comparison group of PC patients not on ADT were included. For included studies, relative risk (RR) was pooled using a random effects model.

Results:
1846 records were screened, of which 19 were found suitable for data extraction (Figure 1). 5 studies including 831 patients had MetS as an outcome, with the random effects model showing a pooled RR of 1.49 ([95% Confidence Interval (CI), 1.01-2.21]; I
2
=59%: p=0.04) for patients on ADT. 12 studies including 409,490 patients examined diabetes as an outcome, and the random effects model showed a RR of 1.40 (95% CI, 1.28-1.54), while 4 studies including 7,051 patients examined hypertension as an outcome, and the random effects model showed a RR of 1.30 (95% CI, 1.08-1.55) in ADT patients.

Conclusions:
ADT was shown to increase the risk of MetS, diabetes, and hypertension in patients with PC undergoing ADT compared to PC patients not on ADT. These results should be understood in the context of collaboration between a patient’s oncologist and primary care provider to optimize care.
Abstract 12769: Association of Lung Protective Ventilation and Outcomes in Patients With Cardiogenic Shock on ECLS
Authors: Tran Lena E , Auvil Bryan , Xu Meng , Huang Shi , Gannon Whitney , Bacchetta Matthew , Shah Ashish S , Balsara Keki , Siddiqi Hasan K , Zalawadiya Sandip , Brinkley D. M , Lindenfeld Joann , Pedrotty Dawn , Menachem Jonathan , Schlendorf Kelly H , Hernandez Antonio , Rali Aniket S
Published: June 2023

Background:
In Acute Respiratory Distress Syndrome, lung protective ventilation (LPV) improves patient outcomes by minimizing the risk of ventilator-associated lung injury. For patients with cardiogenic shock (CS) requiring VA-ECLS, the extracorporeal heart-lung circuit provides a unique opportunity to provide LPV. At present, there are limited data regarding optimal ventilator strategies for patients in CS on VA-ECLS. We hypothesized that CS patients on VA-ECLS who require ventilator support will have better outcomes with LPV.

Methods:
We queried Extracorporeal Life Support Organization (ELSO) registry for hospital admissions between 2009 and 2019 for CS patients on VA-ECLS and mechanical ventilation. Patients with multiple ECLS runs, congenital heart disease, pre-ECLS cardiac arrest, and durable mechanical circulatory support were excluded. We defined LPV as peak inspiratory pressure (PIP24)<30 cm H
2
O at 24 hours on ECLS. ELSO registry does not report tidal volume, hence, PIP24 was used as surrogate for plateau pressure. PIP24 and driving pressure (PIP24 minus PEEP24) at 24 hours (DP24) were also studied as continuous variables. Our primary outcome was survival to discharge. Multivariable analysis adjusted for baseline SAVE score, age, race, BMI, etiology of CS, intubation hours prior to ECMO and history of chronic lung disease.

Results:
A total of 2,226 CS patients on VA-ECLS were included of which 1904 received LPV. LPV patients had a significantly lower BMI (median 28.28 vs 31.14, p<0.001), and were less sick, as assessed by their baseline SAVE score (-1.79 vs -2.79, p=0.002). The primary outcome of survival to discharge was significantly greater in LPV cohort (47.4% vs 32.6%, p<0.001). Median PIP24 (22 vs 24, p<0.001) as well as DP24 (14.5 vs 16, p<0.001) were significantly lower in those surviving to discharge. Adjusted OR for primary outcome with LPV was 1.69 (p=0.0023). Adjusted OR for primary outcome with incremental rise in PIP24 (0.78, p=0.0003) and DP24 (0.75, p<0.0001) were also statistically significant.

Conclusions:
In VA-ECLS patients requiring mechanical ventilation, LPV and lower PIP and DP at 24 hours is associated with improved survival to discharge.
Abstract 12777: The Lingering Snag in Era of Mechanical Pumps: A Case of Acute Pump Thrombosis Immediately After Heartmate 3 Implantation
Authors: Malhotra Anureet , Goyal Amandeep , Dalia Tarun , Farhoud Hassan , Bhyan Poonam , Vidic Andrija , Gupta Bhanu , Shah Zubair , Abicht Travis
Published: June 2023

Background:
Pump thrombosis (PT) remains a dreaded complication of left ventricle assist device (LVAD) implantation. PT immediately after HeartMate 3 (HM3) implantation is rare but should be kelp in mind if early low flow alarms are noted.

Case:
A 57-year-old male with ischemic cardiomyopathy, Stage D heart failure (LVEF ~20%), INTERMACS category 3 on 5mcg/kg/min Dobutamine drip underwent advanced heart failure therapy evaluation and was deemed suitable candidate for LVAD implant. His ECHO showed LVIDD 6.04 cm and LV Diastolic Volume Index 122 mL. He underwent HM3 implantation via left anterior thoracotomy and upper-hemi sternotomy on 5/24/2022. Surgery was successful and the patient was taken off bypass. Pre-implant some LV trabeculations and debris were removed. However, less than 1 hour from being off bypass, the low flow alarms began which did not resolve after volume and blood pressure optimization. No RV failure was noted on TEE. Decision was made to re-open the sternum. Upon exploration, no compression of the outflow graft was noted, and inlet cannula was not mispositioned. Inspection of LVAD inlet and outlet cannula showed significant amount of white thrombus (Figure 1) and device was ultimately exchanged. Thrombus was confirmed on histopathological analysis. Post-operatively no low flow alarms were noted after pump exchange. Factor V Leiden screen and protein C activity were normal and Antithrombin 3 was falsely low (due to recent thrombus) on post-op day 1.

Discussion:
This is the second case of HM 3 device thrombosis within 1 hour of implant in the literature. Most of the earlier reported cases were on post-Op Day 3. The etiology of PT is unknown and further investigation is required to elucidate the same. This case will create awareness among physicians to keep PT in differentials when low flow alarms are encountered immediately post-op despite volume and BP optimization.
Abstract 12778: Improving Advanced Care Planning for Hospitalized Patients With Heart Failure
Authors: Patel Akash H , Runge Ava , Mathew Tobin , De Michelis Nathalie , Mody Behram
Published: June 2023

Introduction:
Advanced Care Planning (ACP) is an important and proven strategy to improve end-of-life communication and the quality of life of patients with heart failure and their relatives. However, the frequency of ACP conversations in practice remains low. UCI’s heart failure (HF) metrics show that in the months of April 2021 to October 2021 prior to intervention, an average of 13.24% of HF patients hospitalized at UCI had completed ACP at discharge, as measured by presence of POLST form or Advanced Directive (AD) in Epic. The goal of this quality improvement project was to determine whether the rate of ACP completion could be improved using electronic medical record (EMR) reminders to the healthcare team.

Methods:
For a 3-month period [January 2022-March 2022], our research team messaged providers designated as ‘First Call’ for each hospitalized patient with a primary diagnosis of HF and no existing ACP documentation in the Epic EMR. Messages were sent via Epic’s secure chat function, serving as a reminder to complete ACP documentation including a POLST form. Messages were sent on the day of admission with a second message sent after 2 weeks if the patient remained hospitalized and there was no change in ACP completion status. Percentage of ACP documentation completion was calculated during the 3-month study period.

Results:
Our results have demonstrated that the ACP completion was an average of 21.00% during the 3 months of the intervention. This is a 7.76% absolute increase in ACP completion compared to 3 months prior to our intervention (13.24%); a 58.61% relative increase.

Conclusions:
ACP among hospitalized HF patients remains low. Direct message reminders to providers serves as a beneficial means of improving ACP completion among this subset of patients.
Abstract 12785: Psat1 Promotes Serine Synthesis Pathway and Cardiac Regeneration After Myocardial Infarction
Authors: Magadum Ajit , Mallaredy Vandana , Roy Rajika , Wang Chunlin , Grace Grace , Cheng Zhongjian , Truongcao May , Joladarashi Darukeshwara , Gurrala Charan Thej , Rigaud Vagner O , Lucchese Anna Maria , Benedict Cindy , Khan Mohsin , Santos Celio X , Shah Ajay M , Koch Walter J , Kishore Raj
Published: June 2023

Introduction:
Permanent loss of cardiomyocytes (CM) after myocardial infarction (MI) and limited cardiac regenerative capacity lead to heart failure. The iPSC-derived extracellular vesicles (EV) have been shown to improve cardiac function and protection. However, the iPSC-EVs-mediated cardiac function improvement mechanism remains unclear and largely pertains to microRNAs and other RNAs, with a little elucidation of the role of iPSC-EV proteins.

Hypothesis:
The myocardial delivery of hiPSC-EV-specific protein PSAT1 (phosphoserine aminotransferase 1) induced cardiac regeneration and improved cardiac function post-MI by activating CM proliferation and anti-oxidative stress molecular pathways.

Methods and Results:
We show that hiPSC-EVs treatment augmented cardiac functions and induced a significant CM cell cycle in mice post-MI. Proteomic analysis identified PSAT1 as a protein expressed exclusively in hiPSC-EVs. The role of PSAT1 in CM proliferation and cardiac regeneration is not studied. The PSAT1 expression was significantly downregulated with heart development. Cardiac delivery of PSAT1 modified mRNA (modRNA) induced a significant CM proliferation post-MI. This increase in the CMs proliferation by the PSAT1 modRNA was associated with reduced scar size, improved cardiac function and CM survival, reduced oxidative stress, and CM apoptosis post-MI. Furthermore, the PSAT1 modRNA inhibited the CM apoptosis by reducing oxidative stress and DNA damage response post-MI. Moreover, we show that the YAP, a master regulator of CM proliferation and cardiac regeneration, binds to the promoter of PSAT1 and induces its expression. Finally, PSAT1 modRNA induced the serine biosynthesis pathway in CMs, resulting in increased nucleotide synthesis and reduced oxidative stress, thereby supporting CM proliferation.

Conclusion:
Our studies uncover a novel role of hiPSC-EV specific protein PSAT1, and serine synthesis pathway activation leads to post-MI CM proliferation, inhibition of oxidative stress, and improved cardiac function. Furthermore, this work emphasizes the therapeutic prospect of using PSAT1 modRNA as a gene delivery approach for ischemic heart diseases.
Abstract 12792: Reentrant Drivers Are Distinguished From Passive Rotors by Sequential Computer Simulation of Ablation Using Personalized Non-Paroxysmal Atrial Fibrillation Heart Models Based on Late Gadolinium Enhancement Magnetic Resonance Imaging (LGE-MRI)
Authors: Sakata Kensuke , Bradley Ryan , Ali Syed Yusuf , Yamamoto Alves Pinto Carolyna , Loeffler Shane , Kholmovski Eugene G , Prakosa Adityo , Trayanova Natalia
Published: June 2023

Introduction:
Although rotor modulation targeting atrial fibrillation (AF) drivers or substrates has been proposed as one of the effective ablation strategies for non-paroxysmal AF (Non-PAF), previous meta-analyses demonstrated that ablation added to pulmonary vein isolation (PVI) did not result in the expected outcome. This is because the optimal method of detection of rotors and ablation strategy remain unclear. Recently, rotor detection using LGE-MRI-based computer simulations has been shown to be effective for Non-PAF ablation in clinical practice. Our study aimed to establish the minimal ablation strategy that, while correctly finding the rotors, also avoids iatrogenic atrial tachyarrhythmias due to excessive ablation.

Hypothesis:
By prioritizing and classifying detected rotors, reentrant drivers (RDs) of AF rather than passive rotors (PRs) could be identified, thereby offering an optimal ablation strategy.

Methods:
Personalized computational modeling of AF ablation was performed in 10 Non-PAF patient models based on fibrosis data from LGE-MRI. In each bi-atrial model, all rotors induced outside of PVI were investigated, and a number of ablation strategies were examined sequentially to classify rotors and achieve minimal ablation (figure). A rotor that terminated following ablation of another rotor was defined as PR. A rotor that persisted and needed to be ablated to achieve non-inducibility of the substrate was defined as RD.

Results:
Seven patients had rotors outside of PVI, with 6 having both PRs and RDs. Overall, 35 rotors were induced, 13 in left atrium and 22 in the right; 17 were RDs and 18 PRs. In addition, the density of fibrosis in the sites of RDs was significantly higher than in those of PRs (p=0.031).

Conclusion:
The sequential computer simulation strategy to predict ablation targets using a personalized AF model is promising in detecting different types of rotors and establishing the optimal minimum-lesion ablation strategy.
Abstract 12797: Obesity Predisposes Pediatric Cancer Patients Treated With Anthracyclines to Subclinical Cardiac Dysfunction Detectable by Strain Echocardiography
Authors: George Ian A , Souder BriAnna , Berkman Amy , Noyd David , Campbell Michael J , Barker Piers , Roth Michael , HILDEBRANDT Michelle , Oeffinger Kevin C , Landstrom Andrew P , McCrary Andrew
Published: June 2023

Introduction:
Anthracyclines are used in > 60% of pediatric cancer cases yet are associated with a life-long risk of cardiomyopathy. Strain echocardiography is currently the standard of care for cardiac surveillance in adult cardio-oncology. However, strain has yet to be widely evaluated in the pediatric population.

Hypothesis:
Strain analysis on echocardiograms from anthracycline-exposed pediatric patients will identify dysfunction that is overlooked by left ventricular ejection fraction (LVEF) alone and which will be associated with identifiable cardiovascular risk factors.

Methods:
All anthracycline-exposed cancer patients < 18 years old with an initial visit to Duke University between 2013-2019 were identified. Subjects with cancer relapses, congenital heart disease, or inadequate imaging for analysis were excluded. Peak longitudinal left ventricular strain was calculated from the 4-chamber view on all adequate surveillance studies for each patient using the TOMTEC AutoSTRAIN software. Univariate and multivariate Cox proportional hazards models were created to identify risk factors for abnormal LVEF (<50%) or abnormal longitudinal strain (>-16%).

Results:
The cohort included 101 subjects (52% male) with 606 echocardiograms for analysis. Median age at diagnosis was 12 years (IQR = 3-15), and median anthracycline dose was 201 mg/m
2
(IQR = 120-284). Median follow-up duration was 3.7 years (IQR = 2.3-5.3). Abnormal LVEF was identified in 5 subjects, while abnormal strain was identified in 16 subjects. All subjects with abnormal LVEF also had abnormal strain. When adjusting for dose, BMI, and family history of cardiovascular disease, anthracycline dose > 250 mg/m
2
and BMI > 25 at diagnosis were predictors of abnormal strain with hazards ratios of 3.3 (p =.02, CI = 1.2-8.9) and 3.2 (P = .03, CI = 1.1-9.5), respectively. Anthracycline dose was the only significant predictor of abnormal LVEF.

Conclusions:
Longitudinal strain is more sensitive than LVEF alone in identifying subclinical cardiac dysfunction in pediatric cancer patients, and those with a BMI > 25 at diagnosis are at an increased risk of dysfunction. Multi-center studies should further explore the link between obesity, early subclinical dysfunction, and subsequent cardiomyopathy.
Abstract 12805: Incidence and Predictors of Myocardial Infarction or Stent Thrombosis in High-Bleeding Risk Patients Undergoing Percutaneous Coronary Intervention
Authors: Nicolas Johny , Spirito Alessandro , Sartori Samantha , Zhang Zhongjie , Pitaro Nicholas , Cao Davide , Vogel Birgit , Beerkens Frans , Youssef David , Jones Davis , Edens Madison , Feldman Daniel , Camaj Anton , Power David , Sweeny Joseph , Sharma Samin K , Kini Annapoorna , Dangas George , Mehran Roxana
Published: June 2023

Introduction:
High-bleeding risk (HBR) patients undergoing percutaneous coronary intervention (PCI) are often at high risk for thrombotic complications following coronary stenting. We sought to evaluate the frequency and predictors of myocardial infarction (MI) or stent thrombosis (ST) events in HBR patients at 1 year after PCI.

Methods:
We included HBR patients undergoing PCI with drug-eluting stent implantation at a tertiary-care center, between 2012 and 2019. HBR status was defined as the presence of ≥1 major or ≥2 minor Academic Research Consortium-HBR criteria. Clinical and angiographic baseline characteristics were analyzed after stratifying patients by the occurrence of MI/ST. Independent predictors of MI/ST at 1-year follow-up were assessed using Cox multivariate regression analysis.

Results:
Among 7,806 HBR patients undergoing PCI, 245 (3.1%) experienced MI/ST within one year of the index procedure. These patients were more frequently female (42.6% vs. 35.7%, p=0.03), had a higher prevalence of insulin-dependent diabetes mellitus (62.3% vs. 40.5%, p<0.001), peripheral artery disease (18.4% vs. 13.4%, p=0.03), chronic kidney disease (57.1% vs. 52.1%, p=0.006), and a history of prior PCI (57.1% vs. 45.7%, p<0.001). Furthermore, they were more likely to undergo complex PCI (43.3% vs. 32.3%, p<0.001) and had a higher mean syntax score (20.6±12.5 vs. 14.2±10.8, p<0.001). Multivessel disease was the most prevalent and strongest predictor of MI/ST at 1-year follow-up, followed by acute coronary syndrome and diabetes mellitus (
Figure
).

Conclusions:
MI/ST events frequently occur in HBR patients undergoing PCI. Predictors of MI/ST must be accounted for while deciding on the optimal antithrombotic therapy strategy in these patients.
Abstract 12818: Microrna Biomarkers Target Genes and Pathways Associated With Type 2 Diabetes
Authors: Kariuki Dorian , Aouizerat Bradley E , Asam Kesava , Kanaya Alka M , Florez Jose , Zhang Li , Flowers Elena
Published: June 2023

Introduction:
Type 2 diabetes (T2D) is a major risk factor for cardiovascular disease (CVD), and CVD remains a leading cause of death among those living with T2D. MicroRNAs (miRs) target messenger RNAs (mRNAs) to alter gene expression, and circulating miRs, which are readily measured from blood, have been studied as potential biomarkers for T2D risk. Our prior analysis of the Diabetes Prevention Program identified a subset of five miRs that were optimal predictors of incident T2D with interactions by trial arm. The purpose of this study was to identify the mRNA and biological pathways targeted by these five miRs to elucidate potential mechanisms of risk and responses to the tested interventions.

Methods:
We obtained experimentally validated human data from miRTarBase (version 8.0), filtered and subsetted the data using R (version 4.1.1) to identify mRNAs with strong evidence of being regulated by the five miRs. Pathway analysis was employed to assess for overrepresentation of the mRNA targets of miRs using the Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation database and clusterProfiler (version 4.2.2) package.

Results:
The five miRs targeted a total of 167 pathways and 122 genes. Among the identified pathways, nine have known T2D associations: Insulin signaling, Insulin resistance, Diabetic cardiomyopathy, T2D, AGE-RAGE signaling in diabetic complications, HIF-1 signaling, TGF-beta signaling, Fatty acid biosynthesis, and Endocrine resistance. Of these, AGE-RAGE signaling was targeted by all five miRs and HIF-1 signaling was targeted by all except miR-144. A total of 36 genes were targeted in the two pathways. Vascular endothelial growth factor A (VEGFA) was targeted by miR-186, miR-203a, miR-205, and miR-206 in both AGE-RAGE and HIF-1 signaling pathways. Among genes that were targeted by two or more miRs, BCL2 apoptosis regulator (BCL2) and VEGFA have prior genetic associations with risk for T2D.

Conclusions:
These findings suggest that miR predictors of incident T2D target mRNAs and pathways known to underlie risk for T2D. Future studies can evaluate miRs as potential therapeutic targets for preventing and treating T2D and for informing mechanisms underlying risk reduction interventions, allowing for more precise treatments for individuals.
Abstract 12824: Predictive Value of Artificial Intelligence-Enabled Electrocardiography in Patients with Takotsubo Cardiomyopathy
Authors: Kanaji Yoshihisa , Ozcan Ilke , Tryon David N , Ahmad Ali , Sara Jaskanwal D , Kakuta Tsunekazu , Lerman Lilach O , Attia Zachi , Lerman Amir
Published: June 2023

Introduction:
Recent studies have indicated high rates of future major adverse cardiovascular events in patients with Takotsubo cardiomyopathy (TTC). This study sought to evaluate the prognostic value of our institutional artificial intelligence-augmented electrocardiography (AI-ECG) algorithms in patients with TTC.

Methods:
This study enrolled consecutive patients in the prospective and observational Mayo Clinic Takotsubo syndrome registry. TTC was diagnosed according to the Mayo Clinic diagnostic. Our clinic’s previously developed and validated AI-ECG algorithms were used for detection of ECG-Age, probability of low ejection fraction, and probability of atrial fibrillation.Multivariable models were constructed to evaluate the association of AI-ECG and other clinical characteristics with major adverse cardiac events (MACE), defined as cardiac death, recurrence of TTC, nonfatal myocardial infarction, hospitalization for congestive heart failure, and stroke.

Results:
In the final analysis, 305 patients were studied over a median follow-up of 4.8 years. Patients with MACE were more likely to be older, have history of hypertension and chronic heart failure (CHF), worse renal function as well as having high-risk AI-ECG findings compared to those without. In the multivariate Cox proportional hazard analysis, the presence of 3 or 4 high-risk findings detected by AI-ECG, remained a significant predictor of MACE in the patients with TTC after adjusted by conventional risk factors (hazard ratio (HR) 2.17, 95% CI [1.33, 3.53], P=0.002; HR 2.44, 95% CI [1.38, 4.29], P=0.002, respectively).

Conclusions:
The combined use of developed AI-ECG algorithms derived from a single 12-lead ECG might identify ECG correlates of underlying non-transient myocardial dysfunction and detect subtle underlying patterns associated with worse outcomes in patients with TTC. This approach might be beneficial for stratifying high-risk patients with TTC.
Abstract 12854: Strategies and Outcomes of Patients With Severely Reduced Ejection Fraction (≤15%) Undergoing Transvenous Lead Extraction: A Single Center Experience
Authors: Arora Yingyot , Carrillo Roger G
Published: June 2023

Introduction:
Patients with severely reduced EF (SREF≤15%) are deferred from transvenous lead extraction (TLE) due to fears of intraoperative hemodynamic collapse. When these patients require lead extraction, their management options are limited, and they suffer high morbidity and mortality. Left ventricular assist devices may provide intraoperative hemodynamic support and facilitate TLE, enabling life-saving interventions.

Hypothesis:
We present our single-center experience performing TLE in 245 patients with SREF. Additionally, we report the outcomes of 8 patients who received left ventricular support during TLE.

Methods:
Between January 2008-January 2022, we performed TLE on 245 patients with Stage D heart failure, SREF, and Class I or II indications for extraction. Primary (clinical success and in-hospital mortality) and secondary outcomes (length of stay [LOS] and procedure-associated complications) were compared between SREF patients and control. A subgroup analysis was performed in the SREF group to evaluate the outcomes of eight patients who underwent extraction with LV assist devices.

Results:
Overall clinical success was high (97.6%), and mortality was low (5.3%). There were no statistically significant differences in primary outcomes associated with extraction between groups. Similarly, there were no significant differences in procedural complications between groups. In the SREF group, there were no significant differences in outcomes between the eight patients undergoing TLE with LV assist devices and cases that did use LV assist devices.

Conclusions:
Lead extraction in patients with SREF can be performed safely and effectively. Adopting a few simple steps, including initiating LV support, can overcome myocardial impairment in patients who decompensate.
Abstract 12855: Matrin-3 Deficiency Exacerbates Hepatic Steatosis and Acute Phase Response
Authors: Cheng Xiao , Baki Vijaya B , Moran Matthew , Li Qingsheng , Sun Xinghui
Published: June 2023

Introduction:
Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide. NAFLD patients have an increased risk of cardiovascular disease. Matrin-3 is a DNA- and RNA-binding protein, and its mutation causes amyotrophic lateral sclerosis in humans. Among these patients, 76% have hepatic steatosis. However, the role of matrin-3 in NAFLD has not been previously studied.

Methods and Results:
We found that matrin-3 expression is induced in fatty livers of humans and mice. Matrin-3 liver specific knockout mice (LKO) displayed increased levels of plasma triglycerides compared with matrin-3 floxed mice, while the body weights of the two groups of mice are similar after 16-week high-fat diet. Moreover, histological staining and triglyceride assay revealed that LKO mice had a 1.57- and 1.58-fold increase in hepatic lipid area and triglyceride levels, respectively, which associate with an increased liver/body weight ratio. Transcriptome and bioinformatics analysis identified 622 differentially expressed genes in LKO livers. Among them, 142 are target genes of constitutive androstane receptor (CAR), a transcription factor controlling the expression of many genes involved in xenobiotic and lipid metabolism. We also found that the expression of CAR and many CAR target genes was reduced in LKO livers. These data suggest that matrin-3 is important in CAR expression and matrin-3 knockout impairs CAR signaling. Interestingly, matrin-3 LKO mice had increased acute phase response and levels of phosphorylated Stat3 in the livers, indicating increased liver injury and inflammation. Mechanistically, impaired CAR signaling reversed the suppression of Plin2, Plin3, and Plin5 proteins that stabilize lipid droplet and inhibit lipolysis, and it reversed the suppression of interleukin 1 receptor type 1 that activates Stat3 signaling in LKO livers. Lastly, CAR expression positively correlates with matrin-3 expression in human livers (r=0.85,
P
=0.0002, n=13).

Conclusion:
matrin-3-CAR axis is an important mechanism to maintain lipid homeostasis and limit acute phase response in fatty livers. It can be potentially targeted to ameliorate hepatic steatosis and inflammation and reduce the risk of cardiovascular disease in NAFLD patients.
Abstract 12864: Nuclear Magnetic Resonance Lipoprotein Particle Subclasses Associate With Chronic Inflammatory Related Diseases Differently Than Cardiovascular Diseases: The Multi-Ethnic Study of Atherosclerosis
Authors: Duran Edward K , Jacobs David R , Pradhan Aruna D , Aday Aaron W , Duprez Daniel A
Published: June 2023

Introduction:
Chronic inflammatory related disease (ChrIRD) is a novel outcome capturing non-cancer, non-cardiovascular clinical events driven by subclinical inflammation. Derangements in triglyceride-rich, low-density, and high-density lipoprotein particle (TRLp, LDLp, HDLp) subclass concentrations known to associate with inflammation and future cardiovascular disease have not been extensively evaluated in ChrIRD.

Hypothesis:
Lipoprotein particle subclasses may predict future ChrIRD in a similar direction and magnitude as with CVD.

Methods:
We measured 17 lipoprotein subclass particle concentrations by NMR spectroscopy in the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is a US cohort including 6,759 White (38.6%), Chinese (11.9%), Black (27.6%), and Hispanic (22%) men and women initially aged 45-84 years and free of CVD. Participants were contacted at least annually to ascertain clinical events. Incident CVD (MI, Stroke, PAD, CV Death) and ChrIRD death/hospitalization risk per-quartile of lipoprotein marker levels were evaluated using disease-specific multivariable Cox regression models adjusted for traditional risk factors.

Results:
Disparate risk associations with ChrIRD and CVD were observed (Figure). Elevated small HDLp, total LDLp, and small TRLp, and were inversely associated with ChrIRD events. Additionally, larger TRLp size was associated higher ChrIRD risk. Metrics of HDL, LDL, and TRL associations with incident CVD as expected. In contrast, Very large TRLp was inverse with both clinical outcomes (HR [95% CI] CVD: 0.83 [0.75-0.96] ptrend=0.09, ChrIRD: 0.85 [0.69-0.99], ptrend =0.02).

Conclusions:
TRL, LDL, and HDL particles differentially associate with CVD and ChrIRD. Established predictors of CVD, including total TRL and LDL particles, small LDL, and large /medium TRL, may be inert or even protective in development of ChrIRD events due to distinct pathophysiologic contributions that warrant further investigation.
Abstract 12879: Endothelial Cu Exporter Atp7a Deficiency Promotes Cu-Dependent Endothelial-to-Mesenchymal Transition and Atherosclerosis via Orchestrating Glycolysis and Ros Signaling
Authors: Ash Dipankar , Youn Seock-Won , Varadarajan Sudhahar , Das Archita , Hou Yali , McMenamin Malgorzata , Boatwright Harriet , Hill Bradford G , Kaplan Jack H , Ushio-Fukai Masuko , Fukai Tohru
Published: June 2023

Introduction:
Oxidative stress, inflammation and metabolic reprogramming contribute to endothelial cell (EC) dysfunction and atherosclerosis. Copper (Cu), an essential micro-nutrient, promotes atherosclerosis via unknown mechanism. Since excess Cu is toxic, bioavailability of intracellular Cu is tightly controlled by Cu exporter ATP7A. However, the role of ATP7A and its molecular linkage with inflammation, oxidative stress and metabolism in EC dysfunction and atherosclerosis are entirely unknown.

Results:
Here we found a dramatic reduction of ATP7A expression in human and mouse atherosclerotic aorta. Surprisingly, ATP7A knockdown (KD) in human aortic ECs using shRNA changed the cell morphology from EC to mesenchymal types. This was confirmed by RNAseq/qPCR showing reduced EC markers and increased mesenchymal markers, indicating endothelial to mesenchymal transition (EndMT). Mechanistically, loss of ATP7A in ECs increased [Cu]i and PFKFB3-dependent glycolysis (1.8- fold by ECAR in Seahorse assay). Overexpression of PFKFB3 or constitutively active PFK2, which enhances glycolysis, or direct Cu treatment induced EndMT. In parallel, ATP7A KD in ECs increased mitochondrial (mito)ROS (9.8 fold)-histone demethylase JMJD2B, which induced inflammatory EndMT inducer TGFβ2-EndMT transcription factor Snail (2 fold) axis. Of note, ATP7A KD-induced glycolysis as well as mitoROS- TGFβ2-Snail axis involved in EndMT were inhibited by Cu chelator TTM. In vivo, Cu transport dysfunctional ATP7A mutant/ApoE
-/-
mice showed enhanced atherosclerosis and CD31
+
/αSMA
+
cells representing EndMT in aorta compared to control ApoE
-/-
mice, which was further confirmed by EC-specific ATP7A
-/-
/mTmG reporter mice.

Conclusion:
Our study demonstrates that ATP7A dysfunction in ECs drives EndMT by orchestrating mitoROS-JMJD2B-TGFβ as well as PFKFB3-glycolysis axis in a Cu dependent manner, leading to Snail induction to accelerates atherosclerosis. Thus, ATP7A is a potential therapeutic target for treatment of inflammatory vascular disease.
Abstract 12880: Left Ventricular Mass Predicts Cardiac Reverse Remodeling in Patients With Type 2 Diabetes and Coronary Artery Disease Who Are Treated With Empagliflozin
Authors: Puar Pankaj , Hibino Makoto , Teoh Hwee , Quan Adrian , Verma Raj , Mazer David , Yan Andrew , Connelly Kim , Verma Subodh
Published: June 2023

Introduction:
Left ventricular (LV) hypertrophy is associated with an elevated risk for cardiovascular disease and all-cause mortality. The cardiovascular benefits of sodium-glucose cotransporter protein-2 (SGLT2) inhibitors have been attributed, in part, to cardiac reverse remodeling. The EMPA-HEART CardioLink-6 study previously reported that SGLT2 inhibition with empagliflozin for 6 months was associated with a significant reduction in LV mass indexed to body surface area (LVMi). We sought to determine in the same cohort if baseline LVMi influences empagliflozin-associated cardiac reverse remodelling.

Methods:
A total of 97 patients with type 2 diabetes and coronary artery disease was randomized to empagliflozin (10 mg/d) or matching placebo for 6 months in the EMPA-HEART CardioLink-6 study. This cohort was stratified into those with baseline LVMi <60 g/m
2
and those with LVMI ≥60 g/m
2
. Between-group comparisons were conducted using a linear regression model adjusted for baseline differences in LVMi (ANCOVA) that included an interaction term between baseline LVMi sub-group and treatment.

Results:
The effect empagliflozin had on the change in LVMi over 6 months was significantly different between patients with a baseline LVMi <60 g/m
2
and those whose LVMi was ≥60 g/m
2
. The adjusted difference between those randomized to empagliflozin and those assigned placebo after multivariable adjustment for baseline characteristics was 0.59 g/m
2
(95% CI: -3.01 g/m
2
, 4.19 g/m
2
, P=0.74) and -7.03 g/m
2
(95% CI: -11.06 g/m
2
, -2.99 g/m
2
, P=0.001) in the LVMi <60 g/m
2
and LVMi ≥60 g/m
2
subgroups, respectively (P
interaction
=0.0054). No significant association was found between baseline LVMi and 6-month change in LV end systolic volume-indexed (P
interaction
=0.086), LV end diastolic volume-indexed (P
interaction
=0.34), or LV ejection fraction (P
interaction
=0.15).

Conclusions:
In the EMPA-HEART CardioLink-6 cohort, greater cardiac reverse remodelling benefits were observed with empagliflozin in patients with higher baseline LVMi. Studies with larger cohorts and longer follow-ups are warranted to confirm the impact baseline LV mass has on SGLT2 inhibitor-associated remodelling.
Abstract 12887: Lightning Strikes Twice - A Case of Light Chain and Attr Amyloidosis
Authors: Prathivadhi-Bhayankaram Sruti , Mansour Shareef
Published: June 2023

The most common subsets of amyloidosis that affect the heart include light chain (AL) and transthyretin (ATTR). While both types cause diffuse amyloid fibril deposition within the interstitial space of the myocardium, they arise from two different precursors. AL amyloidosis results from misfolded monoclonal light chains, whereas ATTR amyloidosis results from misfolded transthyretin monomers. This distinction is essential as it suggests that a diagnosis of one disease does not exclude the existence of the other. We present a unique case of a patient with evidence of both systemic ATTR and AL amyloidosis occurring concurrently.

An 80-year-old male with a past medical history of severe mitral regurgitation S/p mechanical mitral valve replacement, rotator cuff tear, bilateral carpal tunnel syndrome, and multiple hospitalizations for decompensated systolic heart failure was referred to cardiomyopathy clinic. He presented with class III New York Heart Association (NYHA) symptoms, including significant limitations in activity due to dyspnea. An echocardiogram demonstrated severe left ventricular hypertrophy with a low global longitudinal strain, an apical sparing pattern suspicious of amyloidosis. Monoclonal gammopathy workup showed an elevated lambda free light chain. Subsequent bone marrow biopsy demonstrated plasma cell dyscrasia and amyloid deposition in hypocellular bone marrow. Mass spectrometry showed both lambda light chain and transthyretin amyloid protein. He had elevated cardiac biomarkers, speaking for advanced cardiac involvement, together with nephrotic range proteinuria. He was started on chemotherapy/immunotherapy, with daratumumab, bortezomib and dexamethasone. He was in end stage heart failure requiring inotropic support. Few weeks after chemotherapy, he transitioned toward hospice care.

In conclusion, we present a rare case of ATTR and AL amyloidosis coinciding simultaneously that demonstrates the importance of having high index of suspicion for this disease, a stepwise and thorough diagnostic approach highlighting the importance of mass spectroscopy after amyloid protein detection.