bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14540: Allostatic Load/Chronic Toxic Stress and Cardiovascular Outcomes in Breast, Lung and Colon Cancer Patients
Authors: Stabellini Nickolas , Cullen Jennifer , Bittencourt Marcio S , Moore Justin , Shanahan John , Nain Priyanshu , Hamerschlak Nelson , Dent Susan F , Sutton Arnethea L , Tsai Meng-Han H , Banerjee Amitava , Ghosh Arjun K , Sadler Diego B , Montero Alberto , Guha Avirup
Published: December 2023

Introduction:
Cardiovascular disease (CVD) and cancer share a common risk factor: chronic toxic stress/allostatic load (AL). Our previous research found that a 1-point increase in AL is linked to a 25-30% higher risk of major cardiac events (MACE) in prostate cancer patients.

Hypothesis:
Higher AL is associated with increased MACE risk in patients with breast, lung, and colon cancer.

Methods:
Patients ≥18 years diagnosed for the first time with the mentioned 3 cancers of interest between 2010-2019 at a large, hybrid academic-community practice were included in this retrospective cohort study. AL was modeled as an ordinal measure (0-11;
Table 1
). Adjusted Fine-Gray Cox proportional hazard regressions estimated the impact of AL pre- and 60 days post- cancer diagnosis on 2-year MACE.

Results:
Demographic characteristics are summarized in Table 1. Two-year mace MACE occurred in 12.3%, 23.3%, and 9.7% of breast, lung, and colon cancer patients, respectively. Heart failure was the most common MACE, observed in 7.9%, 14.4%, and 4.8% of breast, lung, and colon cancer patients, respectively. Before cancer diagnosis, a 1-point increase in AL raised MACE risk by 11% (aHR=1.11, 95% CI 1.07-1.16) in breast cancer, 18% (aHR=1.18, 95% CI 1.11-1.25) in lung cancer, and 9% (aHR=1.09, 95% CI 1.01-1.18) in colon cancer. After cancer diagnosis, a 1-point increase in AL increased MACE risk by 10% (aHR=1.10, 95% CI 1.06-1.15) in breast cancer and 19% (aHR=1.19, 95% CI 1.12-1.25) in lung cancer, but was not statistically significant in colon cancer (aHR=1.07, 95% CI 0.99-1.16).

Conclusion(s):
Higher AL levels prior to breast, lung, and colon cancer diagnoses are associated with increased MACE risk. Thus, effective implementation of patient-centered communication considering stress levels, stressors, and coping mechanisms is necessary during cardiovascular screening for these cancer patients. Further prospective studies are needed.
Abstract 14541: Pericardiocentesis is Associated With Higher Mortality in Patients With Pulmonary Hypertension
Authors: Vasquez Moises A , Quintero Martinez Juan , Iskander Mina , Uribe Juan , Mijares Ivan A , Luna Alvarez Jose Antonio , mustafa mohammed , Mintz Joel , Noy Jose , de Marchena Eduardo , Alfonso Carlos
Published: December 2023

Background:
Pericardiocentesis in patients with Pulmonary Hypertension (PH) and pericardial effusions has unclear benefits, as it has been associated with acute hemodynamic collapse and increased mortality. Data on in-hospital outcomes in this population is limited.
Aims.
Describe pericardiocentesis-related patient characteristics and in-hospital outcomes in patients with PH versus without.

Methods:
The National Inpatient Sample database was used to identify adult patients undergoing pericardiocentesis during hospitalizations between 2016 and 2020. Data were stratified between patients with and without PH. A multivariate regression model was used to estimate the association of PH with pericardiocentesis in-hospital outcomes, adjusting for statistically significant comorbidities.

Results:
A total of 95,665 hospitalizations with a procedure diagnosis of pericardiocentesis were included, of which 7,770 had PH. Patients with PH tended to be older (67 ± 15.7) and female (56%), had significantly higher rates of hypertension (79% vs 66%, P<0.01), diabetes (26% vs 17%, P<0.01), chronic lung disease (32% vs 23%, P<0.01), chronic liver disease ( 15% vs 12%, P<0.01), CKD ( 44% vs 25%, P<0.01), and chronic heart failure (19% vs 10%, P<0.01). Pericardiocentesis in PH was associated with higher in-hospital all-cause mortality, post-procedure shock, cardiogenic shock, cardiac arrest, and mechanical circulatory support compared to patients without PH. Those presenting with cardiac tamponade had higher odds of mortality, post-procedural shock, and mechanical circulatory support (Figure 1) compared to patients without PH. All P values were < 0.001.

Conclusion:
PH was associated with higher mortality and a higher rate of cardiovascular complications in patients undergoing pericardiocentesis. Those presenting with tamponade had particularly worse outcomes. Further research on the outcomes of pericardiocentesis in these patients is needed.
Abstract 14547: Genetically Predicted Inhibition of HMG-CoA Reductase Reduces Risk of
DNMT3A
Clonal Hematopoiesis
Authors: Carter Paul R , Gozdecka Malgorzata , Quirós Pedro , Lockhart Samuel M , Gray Victoria , Richenberg George , Owen Carina , Jansen Joop , van Bergen Maaike , Larsson Susanna , Huntly Brian , Libby Peter , Clarke Murray C , Vassiliou George , Burgess Stephen , Kar Siddhartha
Published: December 2023

Introduction:
Clonal hematopoiesis (CH) is associated with increased morbidity and mortality from cancer and cardiovascular diseases including heart failure and ischemic heart disease. At present no medications are known to protect from CH. However, leukemia cells with equivalent mutations show sensitivity to statin-induced cell death.

Aims:
To evaluate the association of LDL-C lowering genetic variants at
HMGCR
(the target of statins) with CH risk using two-sample Mendelian randomization.

Methods:
We investigated whether lower LDL-C genetically predicted by 6 variants at
HMGCR
associates with CH risk. Secondary exposures included a polygenic instrument of 74 LDL-C-lowering genome-wide variants. Genetic associations for LDL-C derived from a genome-wide association study (GWAS) meta-analysis of circulating LDL-C levels by the Global Lipid Genetics Consortium (N≤188,578 individuals of European ancestry). Outcome associations for CH were from a GWAS in 368,526 European individuals in UK Biobank.

Results:
Genetically predicted reduction in HMG-CoA reductase activity equivalent to a 38.7mg/dL lower circulating LDL-C level was associated with reduced odds of overall CH (OR 0.75, 95% CI 0.58-0.97,
P
= 0.027) or
DNMT3A
CH (OR 0.64, 95% CI 0.48-0.86,
P
= 0.003) but not
TET2
CH (OR 1.12, 95% CI 0.63-2.00,
P
= 0.70). Associations were consistent across all 6
HMGCR
variants in sensitivity analyses. Co-localization plots showed evidence of co-localization of LDL-C with
DNMT3A
CH and overall CH at the
HMGCR
locus. Associations were stronger for CH with variant allele fraction ≥10%, and, statins suppressed colony formation of mutant
DNMT3A
cells in vitro
,
suggesting statins may limit clonal expansion. In a secondary analysis to explore LDL-C dependence, LDL-C lowering predicted by the polygenic instrument did not associate with overall or
DNMT3A
CH but associated with increased odds of
TET2
CH (OR 1.13, 95% CI 1.01-1.27,
P
= 0.03). Findings were replicated in a non-European cohort.

Conclusions:
Genetically predicted lifelong reduction of HMG-CoA reductase activity was associated with reduced risk of overall and
DNMT3A
-mutant CH, likely by LDL-C-independent mechanisms. This provides a strong rationale for clinical trials testing the effects of statins in CH.
Abstract 14569: Chemotherapy in Pregnancy: Assessing the Safety of Adriamycin Administration in Pregnancy Complicated by Breast Cancer
Authors: Nain Priyanshu , Seth Lakshya , Bell Ashley , Raval Priyanka , Sharma Gyanendra , Sharma Garima , Bethel Monique , Guha Avirup
Published: December 2023

Introduction:
Treatment of Pregnancy Associated Breast Cancer (PABC) with radiation and endocrine therapy is challenging due to potential risks to the fetus. Surgical treatment is safe throughout pregnancy, and chemotherapy agents such as anthracyclines are safe during 2
nd
and 3
rd
trimesters.

Case Presentation:
A 39-year-old G4P3 female presented at 8 weeks gestation with a twin pregnancy and a right breast mass with bloody nipple discharge. Past medical history was significant for obesity and chronic hypertension. Biopsy of the mass confirmed weakly ER+/PR-/HER2-, node+, stage IIb PABC. After radical mastectomy and axillary lymph node dissection, 4 Adriamycin and Cyclophosphamide (AC) based adjuvant chemotherapy cycles q3 weeks were started at 12 weeks of gestation with a maternal and fetal echocardiogram, brain natriuretic peptide and troponin measurements after each cycle. A baseline echocardiogram revealed cardiomyopathy with an LVEF of 45% and a severely dilated left ventricle. She was New York Heart Association class II at baseline. Carvedilol 6.25 mg BID was started prior to beginning AC and titrated to 12.5 mg BID due to palpitations after 1
st
AC cycle. She tolerated 4 AC cycles with no change in EF from baseline, no symptoms of heart failure, and a normal fetal echocardiogram. Weekly Paclitaxel was resumed to complete 12 cycles prior to radiation treatment. She delivered healthy male and female infants at 32 weeks with no complications (M: APGAR 5 and 7; F: APGAR 8 and 7). Postpartum EF decreased to 40%, necessitating titration of carvedilol to 25mg BID and the addition of Sacubitril/Valsartan 24/26 mg BID. Chest pain complaint after delivery prompted evaluation with computed tomography-based angiogram and cardiac magnetic resonance imaging (CMR), ruling out coronary artery disease. Despite this, no evidence of microvascular disease on CMR symptomatic relief was reported on long-acting nitrates.

Discussion:
This case demonstrates the importance of multidisciplinary patient management, particularly for those with low LVEF who are at higher risk of decompensation. Despite not knowing the etiology of PABC, she could be suffering from thrombotic microangiopathy of small coronary vessels, which explains relief from nitrates.
Abstract 14576: Circulating Bone Morphogenetic Protein 10 as a Prognostic Biomarker in Heart Failure: A BIOSTAT-CHF Study
Authors: Ceelen Daan C , Bracun Valentina , van Essen Bart J , Voors Adriaan A , Masson Serge , de Boer Rudolf A , ter Maaten Jozine M , Suthahar Navin
Published: December 2023

Introduction:
Bone morphogenetic protein 10 (BMP10) plays a central role in cardiac embryogenesis and is known to facilitate cardiac repair after myocardial injury in adults. The prognostic value of BMP10 in heart failure (HF) remains largely unknown.

Objectives:
To identify biological processes related to elevated BMP10 concentrations and to investigate the prognostic utility of circulating BMP10 in HF patients.

Methods:
Serum BMP10 concentrations were measured in 2085 chronic HF patients from the European BIOSTAT cohort using a prototype electrochemiluminescence immunoassay developed by Roche Diagnostics. First, we performed gene set enrichment analysis to identify biological pathways related to elevated BMP10. Next, we examined the predictive value of BMP10 for all-cause mortality, HF hospitalization and a combined endpoint of mortality and/or HF hospitalization on top of an established risk score, atrial fibrillation (AF) and stroke using Cox-regression analysis after log-transformation and standardization. Results were validated in an independent cohort of HF patients (n=1487).

Results:
High BMP10 was related to pathways of growth and growth factor activity, regulation of bone, extracellular region, and response to hormones/glucocorticoids. After adjusting for the BIOSTAT risk scores, AF and stroke, log-BMP10 remained a strong predictor of 2-year all-cause mortality (Hazard Ratio [HR] =1.17, Confidence Interval [CI]= 1.06-1.28), HF hospitalization (HR [CI]=1.13 [1.03-1.25]) and the combined endpoint (HR [CI]=1.10 [1.02-1.19]). Similar trends were seen in the validation cohort (Figure 1).

Conclusions:
BMP10 is an independent predictor of HF-rehospitalization and all-cause mortality in patients with HF.
Abstract 14585: Early Right Ventricular Snail Expression is a Druggable Target to Improve Right Ventricular Function in Pressure-Overloaded Right Heart Failure
Authors: Ichimura Kenzo , Mao Yuqiang , Boehm Mario , Ali Khadem , Andruska Adam , Schimmel Katharina , Zhang Fan , Reddy Sushma , Spiekerkoetter Edda F
Published: December 2023

Introduction:
Cardiac fibrosis disrupts the myocardial architecture, impairs the exchange of oxygen and nutrients, and puts the heart at risk of failure. Snail (SNAI1) is a transcriptional factor involved in cell plasticity that has been linked to fibroblast-to-myofibroblast transition (FMT) in the hypoxic heart, however, it is unknown whether inhibition of FMT reduces fibrosis and improves right ventricular (RV) function in the pressure overloaded RV. We hypothesized that Snail is necessary for FMT and, as BMP signaling inhibits Snail, that two BMPR2 activators, FK506 and Enzastaurin, reduce cardiac fibrosis and improve cardiac function in a pulmonary artery banding (PAB) mouse model.

Methods and Results:
We performed PAB surgery on snail-YFP reporter mice and observed transient Snail expression exclusively in the RV 3-7 days after inducing pressure overload (Fig. 1). In PeriostinCre-TdTomato reporter mice we showed that Snail was expressed in proliferating Periostin and vimentin positive fibroblasts representing activated myofibroblasts.
In vitro
, stimulation of cardiac fibroblasts with TGFbeta resulted in the early expression of Snail at 2 hours, followed by a Snail-dependent Acta2 expression after 24 hours and Col1 after 48 hours, suggesting the critical role of Snail in fibroblast activation. Furthermore, application of stretch and pressure (50kPa) to cardiac fibroblasts, mimicking pressure-overload
in vivo
, increased Snail expression. FK506 and Enzastaurin inhibited Tgf-b induced Snail expression in
vitro
as well as
in vivo
when administered immediately after PAB surgery (Fig. 2). Finally, long-term treatment with Enzastaurin resulted in preserved RV function at week 7 as assessed by cardiac MRI (Fig. 3, N=6).

Conclusions:
Snail expression is strongly associated with fibroblast activation in the pressure-overloaded RV. Inhibiting Snail with BMPR2 pathway modulators is a promising approach to improve RV function in the pressure-overloaded RV.
Abstract 146: Advanced Age and Neurological Recovery in Elderly Patients With Out-of-Hospital Cardiac Arrest Treated With Targeted Temperature Management: A Nationwide Population-Based Registry Study
Authors: Kwon Hyojeong , Kim Sang-Min , Kim Youn-Jung , Kim Won Young
Published: December 2023

Objectives:
The chance of neurological recovery after out-of-hospital cardiac arrest (OHCA) can be influenced by advanced age, however further recent evidence will be need in elderly population. The purpose of this study is to evaluate the impact of advanced age on the neurological recovery in elderly OHCA survivors treated with targeted temperature management (TTM).

Methods:
This retrospective observational study, using a nationwide population-based OHCA registry, was conducted from January 2016 to December 2020. Non-traumatic elderly (≥ 65 years) comatose OHCA survivors treated with TTM were enrolled. The elderly patients were divided into four groups (65-69 years, 70-74 years, 75-79 years, and ≥ 80 years). The primary outcome was good neurological outcome, defined as Cerebral Performance Categories (CPC) of 1 or 2 at hospital discharge.

Results:
Among 23,336 OHCA patients who admitted to the hospital, 3,398 patients treated with TTM. Excluding 2,033 non-elderly patients, 1,365 patients were analyzed. In four elderly group, the rate of good neurological outcomes were decreased by advanced age (24.2%, 16.1%, 11.4%, and 5.9%). This was also observed after subgroup analysis based on the initial shockable (40.6%, 31.5%, 28.6%, and 14.9%) and non-shockable rhythm (10.6%, 7.2%, 4.1%, and 3.4%). Multivariate analysis showed the adjusted odds ratio (aOR) for good neurological outcome decreased as advanced age (65-69 years: reference, 70-74 years: aOR 0.70, 75-79 years: aOR 0.49, and ≥ 80: aOR 0.25). The optimal age cutoffs for good outcome in elderly OHCA survivors with shockable and non-shockable rhythm were 77 years and 72 years respectively.

Conclusions:
The neurologic recovery rate in OHCA survivors treated with TTM was gradually decreased with advanced age. However even with ≥ 80 years with shockable rhythm, had a good neurologic outcome of 14.9%, which is higher than 65-69 years of 10.6% in non-shockable rhythm.
Abstract 14618: Comparative Outcomes of Elective Endovascular Abdominal Aortic Aneurysm Repair in Patients With Preoperative Cardiac Stress Testing
Authors: Huttler Joshua J , Jamil Yasser , Pinto Rodriguez Paula , Slade Martin , aboian edouard , Columbo Jesse A , Sinusas Albert J , Velazquez Eric J , Guzman Raul J , Ochoa Cassius I
Published: December 2023

Introduction:
The use of cardiac stress testing (CST) before endovascular abdominal aortic aneurysm (EVAR) repair is controversial. While prior research has explored the utility of CST before EVAR, EVAR outcomes in patients with different CST results have not been studied. The objective of this study is to evaluate EVAR outcomes in patients with abnormal CST.

Hypothesis:
Patients with abnormal CST before EVAR have inferior outcomes compared to patients with normal CST.

Methods:
The Vascular Quality Initiative (VQI) database for EVAR was reviewed. Patients who underwent CST prior to elective EVAR were included. In VQI, abnormal CST is defined as having ischemia, infarction, or both ischemia and infarction (BII). Outcomes of patients with normal and abnormal CST were compared, including a subgroup analysis of CST abnormalities.

Results:
A total of 19,964 patients were included and 23.7% (4,723) had abnormal CST. Patients with abnormal CST were more commonly males with comorbidities. Patients with abnormal CST had significantly more perioperative complications including MACE and one-year mortality compared to patients with normal CST. (
Table
) Regression analysis revealed that abnormal CST was independently associated with increased perioperative MACE (OR=1.59 [1.28-1.97]) and one-year mortality (HR=1.11 [1.00-1.23]). Subgroup analysis of patients with abnormal CST showed that patients with BII had significantly more perioperative MACE (6.8% vs 4.1%,
P
=0.002) and mortality (1.1% vs 0.4%,
P
=0.040) compared to patients with either ischemia or infarction. BII was independently associated with MACE (OR=1.62 [1.06-2.41]) and 30-day mortality (OR=3.28 [1.21-8.16]) compared to either abnormality.

Conclusions:
Patients with abnormal CST have worse outcomes after elective EVAR compared to patients with normal CST, particularly patients with BII. CST is a useful tool for perioperative and long-term risk stratification in patients undergoing elective EVAR.
Abstract 14634: Hybrid vs. Norwood: Analysis of the NPC-QIC Database to Determine Optimal Approach for High-Risk Single Ventricle Patients
Authors: Callahan Connor P , Miller Paighton , Carvajal Horacio , Canter Matthew , Mannie Chelsea , Wan Fei , Hill Garick D , Eghtesady Pirooz
Published: December 2023

Background:
Infants w/ high risk hypoplastic left heart syndrome and variants (HR-HLHS) due to low birth weight or gestational age experience worse outcomes. Optimal management remains unknown. We sought to 1. compare primary Norwood to hybrid strategies in HR-HLHS 2. identify predictors of futility.

Hypothesis:
Primary Norwood offers improved outcomes compared to hybrid strategies. Very low birth weight and other anomalies may represent futility.

Methods:
We reviewed HR-HLHS from the National Pediatric Cardiology Quality Improvement Collaborative database. Patients with birth weight <2.5kg or gestation <35 weeks, and age ≤ 30 days at admission were included (N=398). Norwood (n=225), hybrid (pulmonary artery band (PAB) + ductal stent, n=76), and PAB w/ prostaglandin (PAB/PGE, n=77) were compared. Transplantation referral (n=1) and comfort care (n=19) occurred. Baseline factors, 1-year survival, and stage 2 completion were reviewed.

Results:
Table shows baseline HR-HLHS features. Norwood had higher risk adjusted 1-year survival and stage 2 completion than hybrid strategies, including in < 2.1 kg (Figure). On multivariable analysis, hybrid (HR 2.8), genetic abnormality (HR 1.5), and ECMO (HR: 7.2) were significantly associated w/ decreased 1-year survival and stage 2 completion, while higher birth weight (HR: 1.5) was associated w/ increased stage 2 completion. Less than 25% of HR-HLHS w/ birthweight < 2.1 kg and ≥ 1 genetic abnormality was alive with stage 2 at the end of follow-up.

Conclusions:
HR-HLHS have better outcomes following primary Norwood than hybrid palliation. In patients w/ birth weight < 2.1 kg and genetic abnormalities, hybrid or Norwood may be futile.
Abstract 14658: Echocardiographic Metrics Before Coronary Artery Bypass Grafting Are Associated With Postoperative Kidney Injury in Patients With Preserved Ejection Fraction, and Mean Perfusion Pressure May Mediate This Relationship
Authors: Waldron Natalie , Hahn Virginia S , Lima Joao AC , Goeddel Lee
Published: December 2023

Introduction:
Preserved left ventricular ejection fraction (LVEF) patients often suffer acute kidney injury (AKI) after coronary-artery bypass surgery (CABG). We studied the relationship of relative wall thickness (RWT) and LV filling pressure (E/e’), measured by preoperative transthoracic echocardiogram (TTE), with AKI in this population. As these markers may identify subclinical cardiac dysfunction, we also examined the role of intraoperative hypotension by mean perfusion pressure (MPP).

Hypothesis:
Are LV RWT and E/e’ from preoperative TTE associated with post-CABG AKI in preserved LVEF patients? Are LV RWT and E/e’ associated with hemodynamic instability measured by total minutes of MPP (MAP-CVP) < 60mmHg (1 min. resolution)?

Aims:
We aim to identify novel preoperative TTE markers that provide mechanistic insight (low MPP) to AKI development in preserved LVEF patients undergoing CABG. This could lead to interventions during high-risk surgeries to reduce AKI.

Methods:
We accessed 1343 patient records and used multivariate logistic regression models adjusted for covariates (Fig. 1).

Results:
Mean (SD) age was 65 (10). 170/709 patients had AKI. RWT and E/e' are weakly correlated (r=.15, p=.0075, n=314). Each E/e’ increase associated with AKI, OR 1.11 (1.04-1.19, p=.003). Every 0.1 RWT increase associated with AKI, OR 1.21 (1.02-1.43, p=.031, n=518). Each minute MPP < 60mmHg associated with 0.6% AKI increase (n=714). E/e’ associated with low MPP; RWT did not.

Conclusion:
In preserved LVEF patients, RWT and E/e’ are associated with higher AKI risk after CABG. E/e’ is also associated with intraoperative MPP<60mmHg, which may partially mediate the E/e’-AKI relationship.
Abstract 14664: Integrated Atherosclerotic Cardiovascular Disease Lipid Management Initiative
Authors: Hemmitt Roseanne , Alicki Rebecca , Olson Liz , Overton Katherine , Ndumele Chiadi E
Published: December 2023

Introduction:
In the US, 48.6% of adults ≥40 years of age are eligible for statin therapy. Since the release of updated ACC/AHA guidelines in 2018, statin use and mean low-density lipoprotein cholesterol (LDL-C) levels remained unchanged, suggesting that enhanced efforts to understand and implement guideline-directed therapies are needed.

Objective:
The ASCVD Lipid Management Initiative’s primary goals are to increase the proportion of very-high risk ASCVD patients achieving LDL-C levels < 70 mg/dl and to increase appropriate referrals to lipid management clinics.

Methods:
The AHA has engaged a cohort of six diverse health systems (caring for 40,000 patients) to characterize current clinical lipid management care pathways, identify barriers to treatment and to partner to refine lipid management strategies. The methods of the 3-year intervention focus on implementation science, peer-to-peer learning, and patient engagement.

Results:
In the first 12 months of the intervention, health systems collectively identified several common barriers and developed corrective actions to promote standardization of lipid management (
Table
). Organizations are participating in regular quality improvement discussions with an AHA consultant and attending quarterly ASCVD Learning Collaborative calls to share insights and strategies. This initiative has implemented a Referral to Lipid Management measure in the Get With The Guidelines(R) - Stroke and Coronary Artery Disease registries and piloted an outpatient registry with a focus on ASCVD and risk factor related measures. A unique identifier system is being developed to follow patients from inpatient to outpatient settings, as well as an app to facilitate patient activation.

Conclusion:
Together, AHA and health systems are identifying barriers to lipid management and implementing strategies to optimize ASCVD care pathways. We will evaluate the impact of the intervention on LDL-C and referrals for lipid management.
Abstract 14666: Prognostic Value of Artificial Intelligence-Enabled ECG for Increased Left Ventricular Filling Pressure
Authors: Lee Eunjung , Miranda William , Lopez-Jimenez Francisco , Yu Hee Tae , Friedman Paul , Attia Zachi , Oh Jae K
Published: December 2023

Introduction:
Left ventricular diastolic function and filling pressure (FP) can be assessed by echocardiography and cardiac catheterization. Recently, a novel artificial intelligence (AI)-enabled ECG has proven to be effective in identifying increased FP determined by echocardiographic assessment of diastolic function.

Aims:
We aimed to compare a prognostic value of AI-ECG determination of FP compared to echocardiography and catheterization.

Methods:
This study included 4,213 patients who had a transthoracic echocardiogram and ECG within 30 days before hemodynamic cardiac catheterization. Increased FP was defined as pulmonary artery wedge pressure >15 mmHg by catheterization and grade 2 or 3 diastolic dysfunction by echocardiography based on diastolic function guidelines. Increased FP by ECG was identified using previously developed AI-ECG. AI-ECG performance was evaluated using the area under the curve (AUC) of the receiver operating curve. We assessed the risk of all-cause mortality using Kaplan-Meier estimate and multivariable Cox proportional-hazards models.

Results:
AI-ECG had AUCs of 0.8 and 0.7 for predicting increased FP determined by echocardiography and catheterization, respectively. Death was observed in 2,776 (34%) patients over a median follow-up of 7.7 years (IQR 7.1, 8.3). Survival of patients with normal and increased FP by AI-ECG, Echocardiography, and catheterization are shown in Figure 1a. Concordant diagnoses of normal and increased FP by AI-ECG and catheterization or echocardiography had the highest and lowest survival rates, respectively. When FP by AI-ECG was discordant, survival was better predicted by AI-ECG compared to echocardiography and catheterization (Figure 1b).

Conclusion:
AI-ECG for FP has a potential to discriminate prognosis further compared to FP determined by echocardiography or catheterization.
Abstract 14675: The Role of Biomechanics in Diagnosis and Evaluation of Coronary Artery Disease
Authors: Jalal Sahar , Soriano Lilia , Dornback Alexander , Narula Navneet , Molony David , Samady Habib , Lin Fay , Dunham Simon
Published: December 2023

While there is a strong need to assess the safety and efficacy of novel therapies prior to evaluation in human patients, the ability to accurately model the complexities of coronary disease in-vitro and/or animal models is somewhat limited. Animal models, even those with genetic predispositions toward coronary disease do not exhibit high grade stenoses, similar to those that require treatment in human patients. At the same time, most in-vitro models and simulations of fluid-structure interactions cannot simultaneously capture the complex geometries, hemodynamics, and biomechanical response of human coronary disease. Here, we introduce a robust workflow to replicate an in-vitro platform incorporating compliant, realistic diseased coronary arteries in a flow loop under physiological conditions. Through ex-vivo imaging of cadaveric specimens, coupled with co-registered measurements of coronary biomechanics, we developed protocols that allow for fabrication and testing of highly realistic 3D printed models. The anatomical and biomechanical features of the coronary arteries, including local variations associated with the observed disease burdens were extracted and 3D printed, in high spatial resolution, using commercially available printers, making this methodology conveniently reproducible. Subsequently, the models were incorporated in a testing platform made of flow loops and valve resistance to mimic circulation and microvascular resistance respectively. Under physiological boundary conditions, we successfully collected measurements along the length of the vessels that exhibit a range of biomechanical characteristics from low to high values of modulus and assessed the impact of biomechanics on gold standard diagnostic and prognostic measures such as Fractional Flow Reserve. We demonstrated that incorporating the effects of local biomechanics significantly improves the predicted hemodynamics metrics with respect to ex-vivo coronaries.
Abstract 14677: Surgical Thymectomy for Autoimmune Encephalitis With CRMP-5 and AMPAR Antibodies Induced by SARS-CoV-2 Infection
Authors: Puerta Cristian , Hernandez Moises , Zhang Yu , Onaitis Mark , Boys Joshua , Thistlethwaite Patricia
Published: December 2023

Introduction:
SARS-CoV-2 has been linked to development of autoimmune diseases. We describe a case of a patient with untreated thymoma who developed 2 cross-reactive autoantibodies between thymus and brain: collapsing response mediator protein-5 (CRMP-5) and alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid receptor (AMPAR), triggered by SARS-CoV-2, inducing encephalitis and coma. Emergency thymectomy reduced anti-CRMP-5 and anti-AMPAR antibodies and restored patient neurologic function within 3 months.

Description of Case:
A 31-year-old male with a known history of thymoma with myasthenia gravis presented with a 1-day history of memory loss, hallucinations, ataxia, involuntary movements, and tachypnea. Rapid nasal swab COVID-19 test was positive. Over several hours, the patient became unresponsive, requiring urgent intubation for airway protection. Brain computed tomography and magnetic resonance imaging with gadolinium showed no abnormalities. Cerebrospinal fluid (CSF) analysis revealed leukocytosis with lymphocytic predominance. Four days later, CSF and serum were tested for and demonstrated high levels of CRMP-5 and AMPAR antibodies, consistent with autoimmune encephalitis. Complete robotic thymectomy was performed. Pathologic analysis revealed type B2 thymoma with negative resection margins. Three months after surgical intervention, antibody titers normalized, the patient regained consciousness, and had no neurologic deficits.

Discussion:
Surgical thymectomy effectively treats autoimmune encephalitis in patients with thymoma and positive CRMP-5 and AMPAR antibodies in the setting of SARS-CoV-2 infection. This rare condition is typically seen in patients with thymoma or small cell lung cancer who experience acute viral infection. Although autoantibodies to CRMP-5 and AMPAR are known to be induced by viral infection, this is the first time it has been reported for SARS-CoV-2. Timely surgical intervention is necessary to reverse obtundation and acute encephalitis by removing the cross reactive epitopes in the thymus gland. Future studies are needed to explore the molecular mechanism of SARS-CoV-2 induced immune dysfunction and autoimmunity involving cross-reactive epitopes in this deadly syndrome.
Abstract 14679: Microcirculatory Flow and Resistance at Rest and Hyperemia in Relation to Major Adverse Cardiovascular Events in Chronic Coronary Syndrome
Authors: Shekarestan Shajan , Jokhaji Fadi , Ekenback Christina , Törnerud Mattias , Lorstad Samantha , Ljungman Petter , Östlund-Papadogeorgos Nikolaos , Linder Rickard , Samad Bassem , Persson Jonas
Published: December 2023

Background:
The prognostic implications of coronary microvascular dysfunction in an all-comer cohort with chronic coronary syndrome (CCS) are not known.
Aim:
To investigate the association of baseline resistance index (BRI), index of microcirculatory resistance (IMR), and thermodilution-derived resting- and hyperemic flow velocities (RFV and HFV) with the primary composite endpoint consisting of all-cause mortality, incident myocardial infarction (MI) or hospitalization due to congestive heart failure (CHF) in CCS.

Methods:
CCS patients undergoing elective coronary angiography (CA) were included. Measurements of corrected IMR, BRI and mean transit time at baseline (Tmn
base
) and during hyperemia (Tmn
hyp
) were obtained in the LAD. RFV and HFV were calculated as 1/Tmn
base
and 1/Tmn
hyp
, respectively. Cox-regression was performed and Kaplan-Meier plots were constructed.

Results:
We included 503 patients before the coronary anatomy was known and thermodilution measurements in the LAD were obtained in 413 patients. Median age was 68 (IQR 61-74), 127 (25%) were women and 151 (37%) had a flow-limiting epicardial lesion in the LAD. Median follow-up was 5.3 years (IQR 3.0-6.6) and there were 57 events. Log
10
BRI was inversely associated with the primary endpoint before and after fractional flow reserve (FFR) adjustments (HR 0.64 [95% CI 0.42 - 0.97]; Figure 1A). Log
10
IMR was not associated with the primary endpoint (HR 0.94 [95% CI 0.61 - 1.5]; Figure 1B). Log
10
RFV was associated with the primary endpoint before and after FFR- adjustment (HR 1.8 [95% CI 1.2 - 2.7]) whereas log
10
HFV was not (HR 1.2 [95% CI 0.75-1.8]).

Conclusion:
Low microcirculatory resting resistance and high coronary resting flow velocity in the LAD, indicating impaired autoregulation, were associated with all-cause death, MI and/or CHF in CCS whereas hyperemic microcirculatory resistance and flow were not. Resting flow indices can be used for risk evaluation in patients with CCS undergoing CA.

.
Abstract 14687: Altered Left Ventricular Hemodynamic Forces as an Early Indicator of Disease Progression in Duchenne Muscular Dystrophy
Authors: Kollar Sarah E , Capuano Francesco , Soslow Jonathan H , Loke Yue-Hin , Spurney Christopher
Published: December 2023

Introduction:
Duchenne muscular dystrophy (DMD) patients develop progressive cardiomyopathy. Cardiac magnetic resonance (CMR) imaging can identify global/regional dysfunction and myocardial fibrosis, although left ventricular (LV) biomechanics are not conventionally assessed. Thus, we investigated hemodynamic force (HDF), a novel measurement of the intraventricular pressure gradient, as potential biomarker for myocardial dysfunction in DMD.

Methods:
Prospective, multi-center study of DMD patients and age-matched controls. Feature-tracking (Qstrain, Medis) performed on short/long-axis cine to capture LV wall motion. Novel diffeomorphic mapping used to generate kinematic models and calculate HDF components (apical-basal, lateral-septal, anterior-posterior) throughout the cardiac cycle (
Figure 1A
). HDF was correlated to conventional CMR parameters.

Results:
Thirty-six DMD and 10 controls included with LV ejection fraction (LVEF) 51±6% vs 56±6% (p = 0.037). DMD patients with normal LVEF had altered HDF across multiple points in each axis compared to controls (
Figure 1B
). Twenty-one DMD patients (58%) with LVEF < 55% had lower apical-basal (p = < 0.001), lateral-septal (p = 0.001), and anterior-posterior (p = 0.005) root mean square (RMS) HDF compared to DMD with normal LVEF
(Figure 1C)
. All components of HDF correlated with LV volumetric/strain parameters (
Table 1
).

Conclusions:
Cine-derived HDF are altered in DMD patients. Decreased systolic HDF and delay to peak diastolic HDF may be an early indicator of myocardial dysfunction compared to conventional CMR testing. Future studies will investigate HDF as a biomarker of disease progression.
Abstract 14702: Roles of Atrial Mass Reduction and Gaps on the Anti-Atrial Fibrillatory Effects of Pulmonary Vein Isolation: A Computational Modeling Study
Authors: Hwang Taehyun , Jin Ze , Kim Daehoon , LIM BYOUNGHYUN , Kwon Oh-Seok , Park Je , Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-sun , JOUNG BOYOUNG , LEE Moon Hyoung , Pak Hui-Nam
Published: December 2023

Background:
Although pulmonary vein isolation (PVI) is the basis of atrial fibrillation (AF) catheter ablation (AFCA), the conditional changes of an anti-AF effect and the wave-dynamic mechanism are poorly understood. Therefore, we compared the effects of PVI based on the ablation circumference, width, and number or locations of gaps with or without amiodarone at the same condition in realistic computational modeling of human AF.

Hypothesis:
An anatomical level of PVI and characteristics of the PVI gap would affect the anti-AF effects of the AFCA.

Methods:
We included 50 patients (76.0% persistent AF) who underwent AFCA. Realistic AF modeling reflecting the computed tomography (CT) and the electroanatomical map was performed on each patient. We compared the AF defragmentation rate (DeFR; change to atrial tachycardia (AT) or termination), termination rate (TnR), and changes in the dominant frequency (DF) and the number of phase singularities (PSs) based on the PVI level (antral vs. ostial), PVI width (single vs. 3х width), number and location of 2-mm PVI gaps with or without amiodarone (10mM). We randomly assigned the number and location of the PVI gaps to the AF models.

Results:
The antral PVI had a significantly higher DeFR (p for trend <0.001) and TnR (p for trend <0.001) than the ostial PVI, PVI gaps, or baseline AF. However, there was no difference depending on PVI width. Among the PVI gaps, the DeFR (p for trend<0.001) decreased as the gap number increased. Additional amiodarone increased DeFR (p=0.003) and TnR (p=0.034) and reduced DF (p<0.001) and the number of PSs (p<0.001) with PVI-gap, especially with a single PVI-gap.

Conclusions:
In this realistic computational modeling study with integrated patients’ atrial anatomy and electrophysiology, the atrial mass reduction depending on the anatomical PVI level, number of PVI gaps, and additional antiarrhythmic drug significantly affected the AF maintenance mechanisms.
Abstract 14706: Outcomes of Sports Participation for Black Athletes With Implantable Cardioverter-Defibrillators: Data From the ICD Sports Registry
Authors: Chukumerije Merije , Olshansky Brian , Saarel Elizabeth V , Cannom David , Link Mark S , Ackerman Michael J , Gan Geliang , Lampert Rachel J
Published: December 2023

Introduction:
The ICD Sports Registry demonstrated that many athletes with ICDs can participate in competitive sports without death, failure to defibrillate, or physical injury. However, sudden cardiac arrest is more prevalent and has worse outcomes in Black compared to White individuals in the general population and among athletes. Outcomes of sports participation for Black athletes with ICDs have not been described.

Aim:
To describe the risk of arrhythmia and efficacy of ICDs in Black athletes.

Methods:
This is a post-hoc subgroup analysis of the ICD Sports Registry, which enrolled athletes with ICDs age 10 to 60, participating in organized, competitive sports, and followed them prospectively for four years. The endpoints and methods are reported previously.

Results:
Among the 440 athletes, 15 were Black and 410 white. Among the Black athletes, hypertrophic cardiomyopathy was the most common diagnosis (40%) and 87% were implanted for secondary prevention or syncope (vs 69% in White athletes). Most common sports were basketball (8), softball (4), and running (3), with 7 Black athletes competing on varsity/junior varsity/traveling teams. Among the Black athletes, there were no appropriate shocks during sports, among white athletes, 7% received an appropriate shock during sports. Among Black athletes, there was one appropriate shock event for ventricular tachycardia (7%), a VT storm in an athlete with idiopathic VF, non-sports-related. Among white athletes, 10% received appropriate shocks during non-sports activities. Two Black athletes (13%) received an inappropriate shock, one competition-related (sinus tachycardia) and the other for T wave oversensing at rest, vs 12% of white athletes. There were no sports-related deaths, arrests, or arrhythmia-related injuries in either group.

Conclusions:
Black athletes represented a small subset of the ICD Sports Registry. Reasons for this are unknown, but may include disparities in ICD implantation and/or in research recruitment/ participation. These Black athletes experienced both appropriate and inappropriate shocks as did white athletes. These data do not suggest a signal for harm for competitive sports participation for Black athletes with ICDs but larger studies are needed.
Abstract 14709: Association Between Esophageal and Cardiac Autonomic Dysfunction in Chagas Disease
Authors: Dumont Sandra M , Paixao Gabriela , Marino Viviane S , Nascimento Bruno R , Rocha Manoel Otávio C
Published: December 2023

Introduction:
Chronic Chagas disease (ChD) may manifest as the indeterminate form, or with chronic cardiopathy (CCM), digestive or mixed forms. CCM is characterized by complex arrhythmias and sudden death, linked to autonomic dysfunction. Pathological involvement of the enteric nervous system triggers the development of the digestive form, and esophageal dysmotility may be another surrogate for dysautonomia. We aimed to assess the association between esophageal autonomic denervation and cardiac autonomic dysfunction in individuals in the indeterminate (ICF) and CCM forms of ChD.

Methods:
Consented patients with serological diagnosis of ChD and ICF (
n
= 30) and CCM (
n
= 33) forms were enrolled. All patients underwent esophageal scintigraphy, and esophageal transit time (ETT) and percentage of esophageal emptying (%EE) were recorded. They also underwent 24h Holter monitoring, and heart rate variability (HRV) indices and burden of ventricular extrasystoles (VES) were revised by a cardiologist. The correlation between ETT, %EE and HRV indices ((SDNN (standard deviation of adjacent RR intervals), low and high-frequency power (LFP, HFP(ms)), in addition to the number of VES in 24h was assessed with the SPSS 23 software.

Results:
63 patients were enrolled, 54% women, with mean age of 58 years. Left ventricular ejection fraction was lower in the CCM group (44,0 ± 10,8 vs. 64,9 ± 6,6, p<0.001). Autonomic dysfunction showed a distinct pattern between ICF and CCM, with lower SDNN and LF/HF values in the CCM group (100,0 ± 49,9 vs. 124,6 ± 43,2, p=0.042 and 1,4 (0,9 - 2,2) vs. 4,5 (1,5 - 9,5), p<0.001, respectively). The CCM group also had higher 24h VES values (890,0 (120,0 - 2743,0) vs. 47,0 (1,7 - 395,7), p=0.002). There was significant inverse correlation between ETT and SDNN (ß=-0,449, p=0.001), LFP (ms) (ß=-0.288, p=0.025), HFP (ms) (ß=-0.368, p=0.004) and LH/FH (ß=-0.334, p=0.008) in the total sample. There was also a statistically significant and direct correlation between ETT and VES (ß=0.578, p<0.05) in the total sample.

Conclusions:
ChD individuals with greater esophageal dysmotility showed a decrease in the oscillatory components of HRV and greater arrhythmic density, possibly as a result of more severe sympathetic and parasympathetic cardiac denervation.
Abstract 14714: Long-Term Neurocognitive Safety of LDL-C Lowering With Evolocumab: Open-Label Extension Data From FOURIER
Authors: Zimerman Andre , O'Donoghue Michelle , Ran Xinhui , Im KyungAh , Ott Brian F , Mach Francois , Zavitz Kenton , Kurtz Christopher E , Monsalvo Maria L , Wang Bei , Atar Dan , Keech Anthony , Sabatine Marc S , Giugliano Robert
Published: December 2023

Background:
Concerns have been raised about low LDL-C levels and possible adverse effects on cognition. PCSK9 inhibitors markedly lower LDL-C, yet EBBINGHAUS, a prespecified substudy within the FOURIER trial, did not show adverse cognitive changes with evolocumab over 19 months median follow-up.

Purpose:
To investigate the long-term effects of evolocumab on cognitive function.

Methods:
EBBINGHAUS was a substudy of cognitive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB) within the FOURIER randomized trial of evolocumab vs placebo in patients with established ASCVD. Patients in North America and Europe who completed EBBINGHAUS on study drug were eligible for an open-label extension (OLE) study with evolocumab. The primary endpoint was change in spatial working memory strategy index of executive function score (SWMI) from baseline over time. Secondary endpoints were measures of working memory, episodic memory, and psychomotor speed. A paired t-test was used to compare baseline vs post-baseline scores during OLE.

Results:
Of 1204 patients from EBBINGHAUS, 306 entered the OLE and were treated with evolocumab for a median of 5.1 years. Median achieved LDL-C was 34 mg/dL (IQR 21-50). No significant change in SWMI occurred during the OLE period overall [mean (±SD) change -0.1±2.7, p=0.73] or when stratified by original randomized allocation (
Figure 1A
). For secondary outcomes, one showed no change during the OLE period, two showed small changes (10-15% of SD), but these were directionally inconsistent (one higher, one lower). In 152 patients originally randomized to evolocumab, there was no significant change in SWMI from randomization through long-term follow-up over a median of 6.7 and a maximum of 7.2 years (mean change 0.1±2.6, p=0.66) (
Figure 1B
).

Conclusion:
Evolocumab did not lead to any apparent long-term decline in cognitive function through follow-up extending up to 7.2 years.
Abstract 14720: Persistence and Adherence to Proprotein Convertase Subtilisin/Kexin Type 9 Monoclonal Antibodies and Ezetimibe in Real - World Settings
Authors: Ghazi Lama , Jones Jenna , Colantonio Lisandro , Poudel Bharat , Wen Ying , Wang Zhixin , Chen Ligong , Bittner Vera A , Woodward Mark , Kalich Bethany , Rosenson Robert S , Dhalwani Nafeesa
Published: December 2023

Introduction:
Non-statin cholesterol-lowering therapies (proprotein convertase subtilisin/kexin type 9 monoclonal antibodies [PCSK9mAb] and ezetimibe) have been shown to reduce atherosclerotic cardiovascular disease (ASCVD) events in randomized clinical trials of patients treated with statin therapy. Effectiveness in the real world, however, is contingent on treatment persistence and adherence.

Aim:
To estimate the proportion of patients who were on therapy, persistent and had high adherence at 365 days following the initiation of a PCSK9mAb versus ezetimibe in real-world clinical practice.

Methods:
We included adults initiating a PCSK9mAb (n= 16,588, 44% ≥ 65 years, 56% male, 78% with ASCVD) or ezetimibe (n=83,086, 35% ≥ 65 years, 51% male, 46% with ASCVD) from Medicare and MarketScan commercial health insurance databases between 7/2015 and 12/2019. We assessed 3 outcomes using pharmacy claims within 365 days following initiation (assessment period): 1) percentage of patients on therapy: percentage of patients with medication supply in the last 60 of 365 days following initiation; 2) persistence: not having a gap of ≥ 60 days between the last day of supply from one pharmacy claim and the next claim; 3) high adherence: having a day of supply for ≥ 80% of the 365 days.

Results:
Percentage on therapy, persistence, and high adherence were higher among patients on PCSK9mAb versus ezetimibe at 365 days (Table 1). When, restricted to participants who were persistent at 365 days, adherence to both PCSK9mAb and ezetimibe was high. The adjusted multivariable-adjusted risk ratio [95% CI] for percentage on therapy, persistent and having high adherence to PCSK9mAb versus ezetimibe was: 1.20 [1.18, 1.21], 1.22 [1.20, 1.24], and 1.16 [1.14, 1.18].

Conclusions:
Patients initiating PCSK9mAb were more likely to be on therapy, persistent and with high adherence at 365 days compared to their counterparts who initiated ezetimibe.

Funding: Amgen Inc.