bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14219: Are There Sex Differences in the Imaging Modalities and Early Use of Echocardiography in Elderly Patients With Pulmonary Embolism?
Authors: Mehdipoor Ghazaleh , Jimenez David , Muriel Alfonso , Piazza Gregory , Rosovsky Rachel , Madridano Olga , Lopez-Saez Juan Bosco , Mellado Meritxell , Diaz Brasero Ana María , O'Donoghue Michelle , BERTOLETTI Laurent , Lopez-Jimenez Luciano , Nunez-Fernandez Manuel , Blanco-Molina Angeles , Prince Martin R , Gerhard-Herman Marie , Bikdeli Behnood , Krumholz Harlan M , Monreal Manuel
Published: June 2023

Background:
Sex differences in symptoms of acute pulmonary embolism (PE) in older adults (aged ≥65 years) may correlate with differences in the imaging modality used for confirming PE. It is also unknown if sex disparities exist in early use of echocardiography for prognostication.

Methods:
Using data from RIETE, a prospective multinational registry of patients with venous thromboembolism, we included older adults with acute PE. We compared the diagnostic modalities that were used in women vs men to confirm PE. We assessed the presenting symptoms/signs, thrombus location in patients diagnosed with computed tomography pulmonary angiography (CTPA), and evaluated PE severity according to the simplified Pulmonary Embolism Severity Index (sPESI) and the European Society of Cardiology (ESC) categories. We investigated the use of echocardiography within 3 days of PE diagnosis by sex.

Results:
REITE had 33,462 PE patients ≥65 years old including 19,294 women (mean age: 78.6±7.4 years) and 14,168 men (mean age: 76.1±7.2 years). CTPA was the dominant modality for PE diagnosis in both sexes, although a slightly smaller proportion of women were diagnosed with CTPA (77.1 vs 79.4, P<0.001). There were no sex differences in the proportion of patients presenting with isolated subsegmental PE (5.0%; 99% CI, 4.6-5.5% vs 5.5% 99% CI, 5.0-6.0%). There were no clinically relevant sex differences according to sPESI or the ESC risk categories (Table). Women were not less likely, indeed slightly more likely, than men to undergo echocardiography within 3 days of PE diagnosis (51.1%; 99% CI, 50.3-51.9% vs 48.9%; 99% CI, 48.0-49.8%).

Conclusions:
Slightly greater use of CTPA for diagnosing PE in men compared to women may reflect more chest pain and hemoptysis on presentation in men. However, there is similar illness severity in elderly men and women and minimal disparity in early use of echocardiography after diagnosis for prognostication.
Abstract 14238: Coronary Artery Calcium for Stroke Mortality Prediction: The Coronary Artery Calcium Consortium
Authors: Erhabor John , Boakye Ellen , Dardari Zeina A , Osei Albert D , Obisesan Olufunmilayo , Jha Kunal , Kumar Sant J , Rosanski Alan , Berman Daniel , Budoff Matthew , Miedema Michael D , Johansen Michelle C , Nasir Khurram , Rumberger John A , Shaw Leslee J , Blaha Michael J
Published: June 2023

Introduction:
Coronary artery calcification (CAC) is a noninvasive biomarker of atherosclerotic plaque burden in the general population and predicts coronary heart disease and mortality. This study examined whether CAC predicts stroke mortality independent of established traditional cardiovascular risk factors.

Methods:
We included 66,511 participants (mean age: 54.4±10.6 years; 33.0% women) from the prospective, multi-center CAC Consortium study without stroke or coronary heart disease (CHD). CAC was assessed at the study baseline with a cardiac-gated computed tomography scan and categorized as absent/present and 0, 1-99, 100-299, and ≥300 Agatston Units (AU). To examine CAC as a predictor for stroke mortality, we utilized multivariable-adjusted Fine and Gray competing risk regression models, adjusting for traditional cardiovascular risk factors. For sensitivity analysis, we excluded patients whose death certificates indicated a possible stroke-complication of CHD (excluded, n=8).

Results:
During a mean follow-up period of 12.3±3.9 years, there were 160 stroke deaths. Compared to individuals without CAC, those with CAC >0 AU had a higher incidence of stroke mortality (0.31 vs. 0.06 per 1,000 person-years). After adjusting for traditional risk factors, individuals with CAC had a significantly higher sub-distribution hazard ratio (SHR) for stroke mortality than those without CAC (SHR: 2.17; [95% CI:1.32-3.56). In addition, compared with individuals without CAC, the risk of stroke mortality significantly increased as CAC increased (SHR range:1.77; [95%CI: 1.03-3.05]) - 3.09; [95% CI:1.72-5.54]). The results obtained from our sensitivity analysis were similar (Table).

Conclusions:
CAC was associated with mortality from stroke independent of traditional cardiovascular risk factors. While a marker of coronary atherosclerosis burden, CAC should be considered a risk marker for all types of atherosclerotic cardiovascular disease mortality.
Abstract 14250: Interpretation of Pediatric Cardiopulmonary Exercise Testing: Impact of Socioeconomic Status
Authors: Mistry Maanasi , Gauthier Naomi , Alexander Mark E , Gauvreau Kimberlee , Jenkins Kathy J
Published: June 2023

Introduction:
Peak oxygen consumption (pVO
2
) is a marker of cardiovascular fitness. While anthropometric data are incorporated into predictive equations, like the Cooper equation, social determinants of health are not. We hypothesized that socioeconomic status (SES) has a greater effect than standard demographic values on predicted pVO
2
in a contemporary population.

Methods:
This is a retrospective analysis of maximal cardiopulmonary exercise test (CPET) data from 2010 to 2020 for largely healthy patients age <19 years with BMI percentile (BMI%) between 5-95. Data were sorted by self-identified race, BMI%, and adjusted gross income (AGI) based on IRS zip code data; AGI was used as a surrogate for SES. Mean percent predicted pVO
2
(%ppVO
2
) was compared between groups for each variable. Linear regression was used to adjust for differences.

Results:
A total of 541 CPETs met inclusion criteria. Mean %ppVO
2
was 97% ± 22.6 predicted (p<0.001) with 30% below criterion standard for normal (85% predicted). After excluding unknown AGI and race, 418 CPETs remained. Mean %ppVO
2
was lower for blacks (n=36) and LatinX (n=26) compared to whites (n=333, p=0.007). Mean %ppVO
2
significantly declined as AGI decreased (p<0.001). The differences in %ppVO
2
between racial categories compared to white remained significant when adjusted for BMI% (black r=-7.3, p=0.035; LatinX r=-15.4, p=0.001). However, these differences both decreased in magnitude and were no longer significant when adjusted for AGI (black r=-6.0, p=0.150; LatinX r=-9.3, p=0.055).

Conclusions:
Lower SES correlates negatively with measured cardiovascular fitness and may confound data interpretation. When using normative reference ranges in clinical decision making, providers should recognize that social determinants of health, rather than patient-related factors, may be more related to predicted fitness. Attention should be paid to social inequities when assessing pediatric cardiovascular fitness.
Abstract 14259: Novel Long Noncoding RNA,
Ppp1r1b-LncRNA
, Epigenetically Promotes Myogenic Differentiation Program in Cardiac and Skeletal Myocytes
Authors: Kang Xuedong , Zhao Yan , Touma Marlin
Published: June 2023

Introduction:
Emerged as critical regulators of the transcriptome, the lncRNAs play important roles in cardiac development and might be targeted to treat human cardiomyocyte dysfunction in congenital heart disease. In our work, we identified a novel lncRNA,
Ppp1r1b-lncRNA
, as an essential, functionally conserved, positive regulator of myogenic differentiation.

Hypothesis:
Ppp1r1b-lncRNA
promotes myogenic differentiation program of cardiac and skeletal myocytes via epigenic mechanisms.

Methods:
Antisense oligonucleotides (GapmeR) were used to suppress
Ppp1r1b-lncRNA
. Chromatin immunoprecipitation (CHIP) and chromatin isolation by RNA purification (CHIRP) were used to analyze gene specific histone modification level and lncRNA: chromatin interaction, respectively. RNA pull-down and RNA immunoprecipitation (RIP) were used to identify
Ppp1r1b-lncRNA
: protein interactome.

Results:
By silencing
Ppp1r1b-lncRNA,
skeletal myoblasts and human-induced pluripotent stem cell derived cardiomyocytes (hiPSCs-CMs) failed to develop fully differentiated myotubes. Analysis of GapmeR injected neonatal mouse heart further confirmed the role of
Ppp1r1b-lncRNA
in normal myogenesis. Members of muscle specific transcription factors, including MyoD1 and TBX5, were not induced during myogenic differentiation in the
Ppp1r1b-lncRNA
depleted cardiac and skeletal muscle precursor cells. Histone modification analysis revealed enrichment of H3K27 tri-methylation at
MyoD1
and
TBX5
promoters in GapmeR treated skeletal myoblasts. Furthermore,
Ppp1r1b-lncRNA
was found to bind to Ezh2, and ChIRP analysis revealed enriched interaction of
Ppp1r1b-lncRNA
with
Myod1
and
Tbx5
promoters, suggesting that
Ppp1r1b-lncRNA
induces transcription of myogenic regulatory factors by interacting with the polycomb repressive complex 2 (PRC2) at the chromatin interface. Correspondingly, the silencing of
Ppp1r1b-lncRNA
increased EZH2 binding at promoter regions of myogenic transcription factors.

Conclusions:
Ppp1r1b-lncRNA
promotes myogenic differentiation by inhibiting histone methylation on the promotors of myogenic master regulators via competing for PRC2 binding with chromatin during heart and skeletal muscle development.
Abstract 14263: Asessment of Pulmonary Vascular Reserve Using Pharmacologic Stress Testing in Patients With Fontan Physiology
Authors: Naimi Iman , Desjardins Laurent , Averin Konstantin
Published: June 2023

Introduction:
The presence of pulmonary vascular disease (PVD) may be under-recognized during standard hemodynamic evaluation in patients with Fontan physiology. Assessment of pulmonary vascular reserve (VR) (Δ pulmonary artery pressure/Δ cardiac index) utilizing pharmacologic stress testing could be a better way of identifying PVD in pediatric patients. The objective of this study is to diagnose Fontan patients with PVD utilizing pharmacologic stress testing.

Hypothesis:
Pharmacologic stress testing will unmask Fontan patients as having PVD.

Methods:
Single center record review of cardiac catheterizations with dobutamine administration in Fontan patients from January 2021 to June 2022. Following acquisition of baseline data on room air, a dobutamine infusion was started at 5 mcg/kg/min with dose escalation as needed until an appropriate heart rate response was achieved. Hemodynamics were reassessed at each dose interval, but data are reported at the highest cardiac index (CI). Abnormal VR was defined as > 3 mmHg/l.

Results:
Eighteen Fontan patients (87% male) were included. Median age at the time of catheterization was 14 (IQR 11, 16) years with mean duration of Fontan circulation of 9.9 ± 3.9 years. The primary indication for catheterization was exercise intolerance (65%). Dobutamine administration did not result in a significant change in indexed pulmonary vascular resistance (PVRi) (2.1 ± 0.8 v 2.4 ± 1.31 iWU, p = 0.21) or Fontan pressure (12 [IQR 11, 14] v 14 (IQR 12, 15), p=1.0]. Eight patients had a PVRi ≥ 2.0 iWu at baseline; while 4 (22% of the cohort) had a PVRi < 2.0 iWU at baseline but had an abnormal VR.

Conclusions:
PVD is common in Fontan patients but may be missed in some patients without pharmacologic stress testing. Accurate diagnosis of PVD will allow for optimization of Fontan circulation with pulmonary vasodilators.
Abstract 14273: Obesity Paradox and Its Impact on Heart Failure With Preserved Ejection Fraction (HFpEF) in Geriatric Patients: A 2019 National Inpatient Analysis
Authors: Narula Harshit , Singh Monika , Abrishami Shabnam , Aqeel Mariam , Niaz Rabiya , Yarrarapu Siva Naga S , Saeed Memoona , Mahadevaiah Ashwini , Thota Anjani Kumar , Desai Rupak
Published: June 2023

Introduction:
Several studies have shown obesity to be inversely associated with mortality, the so-called obesity paradox. Although being a major cardiovascular risk factor, patients with morbid obesity are often excluded in HFpEF-related trials. Thus, we aim to evaluate the impact of obesity on major adverse cardiovascular and cerebrovascular events (MACCE) in Hospitalized Geriatric Patients with HFpEF.

Methods:
We queried the National Inpatient Sample (2019) to identify the geriatric admissions (age ≥65 years) with HFpEF. Comorbidities and outcomes were compared between obese and non-obese patients using relevant ICD-10 codes. Adjusted odds and independent predictors of MACCE with obesity were assessed by multivariable regression controlling for confounders.

Results:
Of 1743940 geriatric admissions with HFpEF, 430395 (24.7%) were obese [median age 75[70-80], female 63.1%, white 77.1%]. The obese cohort often consisted of relatively younger, female, black patients and had higher rates of obstructive sleep apnea (34.1% vs. 10.9%), diabetes (50.3% vs. 31.3%), hyperlipidemia (62.9% vs. 56.6%), chronic lung disease (48.2% vs 38.4%) and depression (17.3% vs. 13.4%) than non-obese (p<0.001). Comorbidities including hypertension (OR 2.00), peripheral vascular disease (OR 1.19), chronic kidney disease(OR 1.19) (p<0.001), and metastatic cancer (OR 1.20; p<0.019) were independent predictors for MACCE. The obese cohort had significantly lower adjusted odds (OR 0.82) of MACCE (Obesity Paradox) and all-cause mortality (2.9% vs. 4.6%) (p<0.001). They were more frequently discharged with prolonged hospital stays and higher hospital charges compared to non-obese (p<0.001).

Conclusions:
Obese geriatric HFpEF admissions have significantly lower odds of all-cause mortality and MACCE but higher comorbidity burden and healthcare utilization as compared to non-obese. Hypertension, metastatic cancer, CKD, and PVD were independent risk factors of MACCE.
Abstract 14321: The Role of the Sigma-2 Receptor in Myocardial Ischemia-Reperfusion Injury
Authors: Rastogi Radhika , Li Jing , Marsh Katherine , Zhang Aimee , Guo Lian-Wang , Yang Zequan
Published: June 2023

Introduction:
Pharmacological studies have identified two subtypes of sigma receptors, which are now known to be encoded by different genes. Activation of the sigma-1 receptor (S1R) is reported to protect the heart against myocardial ischemia-reperfusion injury (IRI). The role of sigma-2 receptors (S2R) in myocardial IRI remains unknown.

Hypothesis:
We hypothesize that inhibition of S2R attenuates myocardial IRI.

Methods:
C57BL/6 (WT) and congenic S2R knockout (KO) mice underwent 40 minutes of left coronary artery (LCA) occlusion followed by 60 minutes of reperfusion (40’/60’ IR). At the end of reperfusion, the hearts were harvested for TTC-Phthalo-blue staining to calculate infarct size (IS), denoted as a percentage of the ischemic risk region (RR). S1R agonist, PRE-084, and S2R antagonist, CM-398, were administered before LCA occlusion. Two other groups of WT mice underwent 30 minutes of LCA occlusion followed by 60 minutes of reperfusion (30’/60’ IR), with one control group and another treated with S2R agonist, Z485, prior to LCA occlusion.

Results:
In mice undergoing 40’/60’ IR, ischemic risk regions (RR, % of LV mass) were comparable among all groups. Infarct size (IS, % of RR) was 53±3% in control mice. Both the S1R agonist and S2R antagonist significantly reduced the IS to 37±4% and 38±2%, respectively (
p
<0.05 vs. control). S2R KO mice had significantly smaller IS (32±4% vs. control,
p
<0.05. Figure Panel A). In mice undergoing 30’/60’ IR, ischemic risk regions were comparable among the 2 groups, but IS was significantly exacerbated in the S2R agonist-treated group (42±2% vs. control 25±4%,
p
<0.05. Figure Panel B).

Conclusion:
Contrary to the effect of S1R, activation of S2R during myocardial IRI aggravated infarct size. Inhibition of S2R exerts an infarct-sparing effect. This pathway presents a new potential therapeutic target to attenuate myocardial IRI.
Abstract 14337: Cardiac Computed Tomography for Preoperative Assessment of Valve Morphology in Aortic Valve Repair
Authors: Obase Kikuko , Matsumaru Ichiro , Nakaji Shun , Miura Takashi , Eishi Kiyoyuki
Published: June 2023

Introduction:
A pre-operative assessment of aortic valve anatomy is important in valve repair for aortic regurgitation (AR). Although echocardiogram provides precise information, clear visualization of entire aortic valve and accurate quantification of valve geometry are limited even with 3D transesophageal echocardiography. In this study, usefulness of cardiac computed tomography (CT) in the evaluation of aortic valve pathology was investigated.

Methods:
A total of 119 patients who underwent surgical treatment for severe AR from May 2016 to July 2021 and had preoperative CT were studied. From the CT data set, volume rendering movie image was reconstructed to visualize valve anatomy. Effective height (EH) and geometric height (GH) were measured by CT in diastole and compared to intraoperative measurements.

Results:
The quality of CT image was satisfactory in 100 patients (84%), acceptable in 17 patients (14%) and suboptimal in 2 patients (2%). CT could visualize such detailed anatomy as shown in the Figure. EH in 41 patients and GH in 67 were measured by both CT and surgery. The measurements showed a correlation in EH (r=0.79, p<0.0001) and in GH (r=0.74, p<0.0001) with minimal bias of -1.6 mm in EH and 0.4 mm in GH and narrow limits of agreement from -5.9 to2.6 mm in EH and from -3.7 to 4.6 mm in GH. Inter- observer variabilities in CT measurement of EH and GH were 3.8±2.9% and 2.6±1.8%, with interclass correlation coefficients of 0.997 and 0.980, respectively.

Conclusions:
Reproducibility of CT measurement was excellent, while there was a little discrepancy between CT and surgical measurement. Not all cases underwent intraoperative measurement, and cases with structurally complexity tended to have surgical measurement. Some errors may be included in also intraoperative measurements. CT feasibly visualized aortic valve en-face view with showing the etiology of AR, which gave useful information to surgeons who perform aortic valve repair.
Abstract 14356: Machine Learning for Detection of Presence and Severity of Aortic Stenosis From B-mode Ultrasound Images: Results of a Blinded Clinical Trial
Authors: Poilvert Nicolas , Goldstein Steven , Lang Roberto M , Phelan Dermot , Rubenson David , Temple-Wong Michele , Kloster Thomas Yngvil , Martin Randolph P , Thomas James
Published: June 2023

Introduction:
Aortic stenosis (AS) is common, with >= moderate severity ~10% above age 75. Despite new therapies, many with AS go undiagnosed due to lack of echo availability and untreated due to improper interpretation. To expand AS diagnosis, we developed an artificial intelligence (AI) algorithm to characterize AS from routine B-mode echo exams without Doppler (AutoAS).

Methods:
80,000 de-identified clinical echoes were assembled spanning none, mild, moderate, and severe AS. About 30,000 of these were used to train a convolutional neural network (CNN) using labels derived from a cluster analysis of maximal jet velocity, mean AS gradient, and aortic valve area (AVA). Once labeled, we extracted all available B-mode clips from parasternal long-axis, short axis at aortic level, and apical 5-chamber views, irrespective of image quality. A spatiotemporal CNN was trained to return a probability distribution for none/mild/moderate/severe AS. To assess performance of the model, a hold-out test set of echoes uniformly distributed over patient sex and AS severity was used. Three Level 3 echo trained cardiologists blindly read the complete Doppler echoes and agreed to call AS severity by AVA (< 1 cm2, severe; 1.0-1.5 cm2, moderate; > 1.5 cm2 but restricted, mild; no restriction, none). Results were also dichotomized into none/mild and moderate/severe AS.

Results:
40 cases comprised this initial test set. Consistency among the readers was outstanding, with κ = 0.95. The table shows the confusion matrix between AutoAS and panel reads, with excellent accuracy (κ = 0.90). Dichotomous results were also outstanding with sensitivity to detect moderate/severe AS of 91% and specificity of 94%.

Conclusions:
AI can identify AS from 3 B-mode views and characterize AS severity with accuracy highly congruent to an expert panel using full Doppler data. This may allow AS to be detected in low-resource and screening settings. Further assessment with a larger hold-out test set is planned.
Abstract 14370: Significant Heterogeneity in Antiplatelet Regimen for Spontaneous Coronary Artery Dissection: A Report of the ISCAD Registry
Authors: Gornik Heather L , Wood Malissa , naderi sahar , Leon Katherine , Gibson C M , Chi Gerald C , Grodzinsky Anna , Wells Bryan , Taylor Angela , Kadian Dodov Daniella , Henkin Stanislav , Norris Samuel , Reyes Cassandra , Alkhalfan Fahad , Vitarello Clara , Kim Esther S
Published: June 2023

Introduction:
Dual antiplatelet therapy (DAPT) is standard for patients (pts.) with acute coronary syndrome due to atherosclerosis. Evidence to support DAPT vs single antiplatelet therapy (SAPT) for spontaneous coronary artery dissection (SCAD) is limited.
Hypothesis:
Prescription of DAPT vs SAPT varies among specialized centers for SCAD.
Methods:
Analysis of 505 pts. with complete patient questionnaire, case report form, and angiography review enrolled in the iSCAD Registry from 9 sites with
>
20 pts. enrolled. Data are presented for 442 pts. with complete medication data who received DAPT or SAPT during index hospitalization (HOSP) and continued at discharge (DC).
Results:
Patient age 49.6
+
10.2 years, 83% were female. Presentation of SCAD: NSTEMI (55.9%), STEMI (26.9%), unstable angina (13.8%), cardiac arrest (4.3%), cardiogenic shock (0.2%). Most common SCAD location was the LAD (60.9%); 20.8% had multivessel SCAD. Management was: medical therapy (75.2%), PCI (22.5%), CABG (1.4%), or PCI + CABG (0.92%). During HOSP 70.1% (317/452) were treated with DAPT vs 29.9% SAPT (135/452). At DC, 74.7% were prescribed DAPT (339/442) vs 25.3% SAPT (112/452). In multivariable analyses, only PCI as SCAD treatment was associated with DAPT during HOSP (OR 3.57, 95% CI 1.90-6.70) or DC (OR 4.9, 95% CI 2.28-10.53). There was significant heterogeneity of antiplatelet regimen across sites ranging from 34.0%-87% DAPT during HOSP (p<0.0001) and 53.8%-83.6% DAPT at DC (p=0.0011) (Figure). There was a trend of recurrent MI among pts. treated with DAPT vs SAPT during HOSP that did not achieve statistical significance (7.1% vs 3.0%, P=0.09).
Conclusion:
In the iSCAD Registry, most pts. with SCAD were treated with DAPT during index HOSP and DC with significant heterogeneity across sites. PCI during index HOSP was associated with DAPT (vs SAPT) prescription. Further study of outcomes, including recurrent MI, with DAPT (vs SAPT) during hospitalization and subsequent follow-up is needed.
Abstract 14401: A Rare Case of Patent Foramen Ovale Thrombus Caught in Transit
Authors: Buttar Rupinder , Rai Devesh , Pandey Ritambhara , Rao Mohan , baibhav bipul
Published: June 2023

Introduction:
Patent foramen ovale (PFO), seen in about 20-25% of the population, is linked with paradoxical embolism. However, a paradoxical thrombus seen in transit through a PFO is an extremely rare finding.

Case:
An 80-year-old-female with a history of stroke, atrial fibrillation (AF), and diabetes presented with a complaint of dizziness. She had a history of non-compliance with her anticoagulation for AF. EKG showed AF with rapid ventricular rate. An echocardiogram showed a large mobile thrombus in both atria representing a paradoxical embolus in transit caught in PFO (Figure A). Right ventricular systolic function was noted to be severely reduced. A transesophageal echocardiogram confirmed a paradoxical embolus in transit with a large amount of mobile thrombus in the left atrium (Figure B, C). Large saddle acute pulmonary embolus, extending bilaterally into main, lobar, and segmental pulmonary arteries, was seen on the CT chest (Figure D). Lower extremity ultrasound revealed right popliteal vein thrombosis extending to the peroneal vein. Due to a high risk of paradoxical systemic embolism patient underwent emergent surgical thrombectomy along with the closure of PFO.

Conclusion:
Paradoxical thrombus in transit through PFO carries a high risk of systemic embolism. Therapeutic options for patients include cardiac surgery with thrombectomy, thrombolysis, or systemic anticoagulation, with no clear consensus regarding the best treatment option.
Abstract 14430: Sex Differences in Heart Transplantation - Analysis of the National Inpatient Sample 2012-2019
Authors: Dewaswala Nakeya , Bhopalwala Huzefa , Minhas Abdul M , Villegas-Galaviz Josue , Arshad Samiullah , Bhopalwala Adnan , Dani Sourbha , Kolodziej Andrew , Michos Erin D , Birks Emma , Vaidya Gaurang
Published: June 2023

Introduction:
Advanced heart failure therapies and heart transplantation (HTx) have been underutilized in women. Therefore, we aimed to explore the clinical characteristics and outcomes of HTx by sex.

Methods:
We conducted a retrospective analysis of adult discharges from the National Inpatient Sample (NIS) between 2012 and 2019. International Classification of Disease (ICD) procedure codes were used to identify those who underwent HTx.

Results:
A total of 20,180 HTx hospitalizations were identified from 2012-2019. Among them, 28% were female. Women undergoing HTx were younger (mean age 51 vs. 54.5 years, p<0.001). HTx hospitalizations among men were more likely to have atrial fibrillation, diabetes, hypertension, renal failure, dyslipidemia, smoking, and ischemic heart disease. HTx hospitalizations among women were more likely to have hypothyroidism and valvular heart disease. HTx hospitalizations in women were associated with no significant difference in risk of in-hospital mortality (adjusted odds ratio [OR] 0.82; 95% confidence interval [CI] 0.58-1.16, p=0.271), no significant difference in length of stay or inflation-adjusted cost as shown in the Table. Men were more likely to develop acute kidney injury during HTx hospitalization (69.2% vs. 59.7%, adjusted OR 0.71, 95% CI 0.61-0.83, p<0.001).

Conclusions:
HTx utilization is lower in women. However, most major in-hospital outcomes for HTx are similar between the sexes. Further studies are need to explore the causes of lower rates of HTx in women.
Abstract 14446: Bcl-x Short Isoform is Essential for Maintaining Multiple-Tissue Homeostasis
Authors: Keller Mariko , Nakamura Michinari
Published: June 2023

Regulated cell death is an essential piece of normal development and maintenance of tissue homeostasis, wherein BCL2 like 1 (BCL2L1) protein is involved in key signaling pathways. Alternative splicing in exon 2 of
Bcl2l1
produces Bcl-x short (Bcl-xS) isoform. However, mutations in around 5’ splice site are classified as variants of uncertain significance in humans, and the isoform-specific role of endogenous Bcl-xS remains largely unexplored. Here we show the role of Bcl-xS
in vivo
by generating the mice with a mutation in 5’ splice site of the
Bcl2l1
that inhibits Bcl-xS alternative splicing. Although loss of BCL2L1 leads to embryonic lethal with massive cell death, Bcl-xS knockout (KO) mice were born at a mendelian ratio and showed no overt abnormality until 3 months of age. Thereafter, the KO mice developed cardiac hypertrophy (heart weight/tibia length, 8.59+/-0.308 vs 11.61+/-0.631,
p
= 0.0005 and 2.13-fold increase in individual cardiomyocyte size,
p
= 0.0001) with contractile dysfunction (EF, 69.25+/-1.31 vs 56.57+/-3.07,
p
= 0.0028) and splenomegaly (spleen weight/tibia length, 5.32+/-0.25 vs 7.12+/-0.49,
p
= 0.0051) at 6 months of age. Despite that overexpression of Bcl-xS induced cell death in cardiomyocytes (2.497-fold compared to LacZ,
p
< 0.0001), there was unexpectedly no overt difference in the level of apoptosis in the KO heart (TUNEL, 0.033+/-0.003 vs 0.030+/-0.002 %,
p
= 0.359), but fibrosis was significantly increased in the KO heart (1.602+/-0.095 vs 2.340+/-0.145 %,
p
= 0.0017). Diabetes was not evident in the KO mice (blood glucose, 169.8+/-10.9 vs 153.3+/-8.46 mg/dl,
p
= 0.2595). Mechanistically, we found that the Akt/mTOR and JNK/cJun signaling are activated in the KO heart and the JNK/cJun signaling is activated with increased Bax expression in the KO spleen. These results suggest that Bcl-xS may be dispensable for development, but is essential for maintaining homeostasis of multiple organs, especially cardiosplenic network, in a tissue-dependent mechanism.
Abstract 14466: Recurrent Heart Block Due to Cardiac Sarcoidosis in a Patient With Interrupted Glucocorticoid Therapy
Authors: Nagamine Todd , Techasatian Witina , Ali Mohammed , Gozun Maan Kathryn , Benavente Kevin , Kuniyoshi Jason , Yeo Jihun , Zhang James , Shah Parthav , Banerjee Dipanjan
Published: June 2023

Background:
Cardiac involvement is a major cause for mortality in patients with systemic sarcoidosis. Atrioventricular (AV) block caused by inflammation involving the conduction system is one of the major manifestations of cardiac involvement. The mainstay of management is immunosuppressive therapy and device implantation if high degree AV block is present. However, there is lack of evidence regarding the appropriate dose and duration of corticosteroids in the treatment of cardiac sarcoidosis.

Case summary:
We describe the case of a 62-year-old man who presented with symptoms of dyspnea and bradycardia and was found to be in second degree AV block type II. Computed tomography of the chest showed hilar lymphadenopathy. Echocardiography revealed reduced systolic function (LVEF of 35-40%). A FDG-PET scan showed hypermetabolic activity of the interventricular septum and pericardium consistent with sarcoidosis. Bronchoscopy with BAL and EUS biopsies revealed necrotizing granulomas consistent with pulmonary sarcoidosis. ICD/pacemaker implantation was discussed; however the patient deferred and ultimately underwent Boston Scientific ILR placement to monitor for arrhythmias. He was started on methotrexate and prednisone with improvement in heart rate from 2:1 AV block (rates 30's) to sinus rhythm with rates in the 60's. Subsequent stress testing demonstrated improvement in heart rate with exercise to 113 bpm. His AV block had decreased in frequency per Implantable loop recorder (ILR) monitoring. A month later, the patient stopped taking prednisone and methotrexate and developed a symptomatic recurrence of 2:1 AV block. He then underwent dual chamber pacemaker implantation with ILR explant.

Discussion:
This case highlights the importance of maintaining and educating patients about long term immunosuppressive treatment in cardiac sarcoidosis to prevent recurrence of conduction abnormalities. The initial dose for those receiving prednisone is typically 40mg daily, while for those patients receiving an additional immunosuppressive agent, the initial dose can be 20mg daily. Based on response to treatment after 1 to 3 months, immunosuppressive therapy should be continued for an additional 9 to 12 months.
Abstract 14471: Cardiac Sarcoidosis Presenting With Hiccups - A Case Report
Authors: Cancarevic Ivan , Ghallab Muhammad , Idrees Zarwa , O'Brien Tracey , Compas Frantzcess
Published: June 2023

Introduction:
Sarcoidosis is a multi-system disorder of unknown etiology that is commonly associated with hilar lymphadenopathy and granulomas. Cardiac involvement is less common, however, sarcoidosis is a known cause of restrictive cardiomyopathy. It typically presents as new-onset arrhythmias or heart failure, although cases of sudden cardiac death have been reported.

Case presentation:
We present a case of a 56-year-old male with a known history of pulmonary sarcoidosis, not on any active treatment, who presented to the emergency department with one week of continuous hiccups every few seconds associated with non-exertional dyspnea. Initial CT scan of the chest showed multiple stellate-like ground-glass opacities and progression of bronchiectasis. Troponins were negative. On the initial EKG, he was found to be in atrial flutter and was admitted to the general medical floor. He was given baclofen and the hiccups resolved over the next 24 hours. Cardiology was consulted for suspected cardiac sarcoidosis and they recommended transferring the patient to the tertiary care center for further evaluation. Upon arrival, the patient underwent catheter ablation for atrial flutter and he returned to the sinus rhythm after the procedure. The initial nuclear scan with gallium was not suggestive of cardiac sarcoidosis, however, subsequent cardiac MRI showed cardiac involvement. Due to the high risk of arrhythmias, the patient was scheduled for implantable cardioverter defibrillator placement before discharge. Treatment with steroids was deferred until after the PET scan could be completed. The patient was discharged in stable condition and interrogation of the device found it to be well functioning and with no significant arrhythmias noted.

Conclusions:
Presentation of cardiac sarcoidosis can be variable and should be considered in any patient with a known history of sarcoidosis who presents with atypical symptoms at or above the level of the diaphragm, such as hiccups or with new-onset arrhythmias.
Abstract 14474: The Levels of Serum Insulin-Like Growth Factor Binding Protein (IGFALS) Decline Seven Days After Non-Emergent Cardiac Surgery - A Potential Link to Neuroinflammation?
Authors: Laudanski Krzysztof , Karwoski Jake , Shin Susan
Published: June 2023

Introduction:
Inflammatory response and metabolic derangements may accelerate neurodegeneration after cardiac surgery. Insulin, insulin growth factor (IGF), and insulin-like growth factor binding protein acid labile subunit (IGFALS) are the centerpieces of glucose metabolism, the critical factor determining long-term recovery from cardiac surgery and neurodegeneration progression[1]. IGFALS is a regulatory element of IGF that increases their half-life and vascular localization

Hypothesis:
We investigate the dynamics of IGFALS up to 3 months after cardiac surgery. We hypothesize that post-cardiac surgery IGFALS serum level abnormalities are related to changes in neuroinflammatory (BDNF, CXCL13) and neurodegeneration marker (tau).

Methods:
Patients (n=25) scheduled for non-emergent heart surgery were included, except for patients with pre-existing immunological aberrancies. Blood was collected before surgery(t
baseline
), 24 hours later(t
24h
) after the first sample, 7 days(t
7d
), and 3 months(t
3m
) after t
baseline
. Variables regarding the surgery were collected from medical records. IGFALS levels were measured via ELISA, while neurodegeneration and neuroinflammation markers via multiplex technology.

Results:
Demographic variables had limited effects on IGFALS. The serum levels of IGFALS varied significantly (H[4;221]=9.146; 0.0274) (Figure 1). The serum levels were significantly lower at t
7d
but recovered at t
3m
. During the acute inflammatory response at t
24h
IGFALS, serum levels remained unaltered. BDNF at 3m correlated with IGFALS at t
7d
(

r
2

=0.38;p=0.012) and t
3m
(

r
2

=0.39;p=0.018). CXCL13 demonstrated similar interactions. Tau level did not correlate with IGFALS dynamics.

Conclusions:
The data demonstrated a significant long-term decline in IGFALS level after cardiac surgery. The correlations suggest a potential link between IGFALS and some neuroinflammatory markers. 1. Westwood, A.J Neurology, 2014.82(18): p. 1613-9.
Abstract 14479: Prolonged Decrease in Endothelial Cell (EC)-Specific Mitochondrial ROS Results in Mitochondrial Dysfunction in Coronary EC and Cardiac Hypertrophy in Post-AMI Animals
Authors: Brinck Teixeira Rayane , Zhang Peng , Sellke Frank W , Abid Ruhul
Published: June 2023

Introduction:
Reducing mitochondrial ROS (mito-ROS) has been a novel approach for improving cardiac function. Here, we evaluated the effect of prolonged decrease in EC-specific mito-ROS on post-acute myocardial infarction (AMI) coronary angiogenesis and cardiac function.

Hypothesis:
We hypothesized that a prolonged decrease in EC-specific mito-ROS contributes to mitochondrial dysfunction in coronary EC resulting in post-AMI maladaptive cardiac remodeling.

Methods:
We used an EC-specific, tetracycline-controlled, transgenic MnSOD overexpression (MnSOD-OE) model. After 16 weeks of MnSOD-OE, mice underwent ligation of left anterior coronary artery (AMI). 28 days post-AMI, ejection fraction (EF), fractional shortening (FS), and left ventricle (LV) mass were determined by echocardiography (n=8/group). Isolated mouse heart ECs (MHEC) were evaluated by Seahorse for mitochondrial function and by western blot for cell signaling. Data were analyzed by Student’s t test. A
p
-value ≤0.05 was considered statistically significant.

Results:
MnSOD-OE mice showed 33% decrease (44.4±2.3 vs. 29.7±3.5) in EF and 35% decrease (21.7±1.2 vs. 14.2±1.7) in FS, compared to control. LV mass was increased by 51% (76.4±1.8 vs. 115.1±12.33 mg) in MnSOD-OE heart. LV end systolic and diastolic areas were increased in MnSOD-OE, by 2-fold (5.8±0.4 vs. 12.6±1.8) and 1.7-fold (9.8±0.5 vs. 16.8±1.6 mm
2
), respectively. MnSOD-OE MHEC showed a reduction in mitochondrial maximal and spare respiration capacities, and decreased activation of Akt by 25% and ERK by 23%.

Conclusions:
Prolonged MnSOD-OE impaired mitochondrial respiration and inhibited Akt and ERK signaling in MHEC. These changes were associated with maladaptive remodeling post-AMI, including cardiac hypertrophy, LV dilatation, and systolic dysfunction. Together, these findings suggest that prolonged decrease in mito-ROS has detrimental effects on coronary EC resulting in maladaptive post-AMI cardiac remodeling.
Abstract 14487: Evaluation of Phenotype and Interaction of Endothelial Function at Different Arterial Levels by Simultaneous Measurement of Flow-Mediated Dilation and Endo-PAT; FMD-J B Study
Authors: Masaki Nobuyuki , Takase Bonpei , Adachi Takeshi K ,   FMD-J Study Group
Published: June 2023

Introduction:
Two representative tests of endothelial function, flow-mediated dilation (FMD) and reactive hypermia index (RHI), often give contradictory results.

Hypothesis:
Simaltaneous evaluation of the interactions and discordances between two tests of endothelial function for different site might clarify the reasons for the contradictory results.

Methods:
A total of 966 patients were enrolled in this study. Simultaneous measurement of FMD and RHI by forearm cuff occlusion was repeated every 1.5 years during a 4.5-year observation period. Test results were divided by 4% of FMD and 1.67% of RHI, and the patients were classified into 4 groups. Lifestyle and blood laboratory values were also assessed at each examination. Data were analyzed on both a test-based and patient-based basis.

Results:
In a total of 1434 tests, there was little relationship between FMD and RHI. Blood glucose levels were negatively correlated with increased brachial artery blood flow velocity after cuff occlusion release (r = 0.095, p < 0.001). Increased blood flow velocity correlated with RHI (r = 0.144, p < 0.001), suggesting that there is an interrelationship between upstream and peripheral blood flow and that hyperglycemia worsens these flows. In addition, delayed time to peak diastole was associated with lower RHI (r=-0.111, p<0.001). Patient-based analysis showed that age, low-density lipoprotein cholesterol, and high-sensitivity CRP were highest in the low FMD/low RHI group, and fasting blood glucose was lowest in the high FMD/RHI group. Antihypertensive medication use, alcohol consumption, and smoking were highest in the low FMD/PAT group.

Conclusion:
The composite assessment by FMD and RHI is useful to indicate the pathological phenotype of endothelial dysfunction. The group with both low FMD and low RHI were found to be at higher risk. In addition, some FMD components were associated with RHI rather than FMD. A subgroup of patients with benign FMD, but with deteriorated RHI, had a longer time to reach maximal dilation. This possibility should be noted when assessing cardiovascular risk based solely on FMD.
Abstract 14496: NOX2 Inhibition Reverses Atrial Remodeling Caused by Increased Oxidative Stress and Reduces AF in Diet Induced Obese Mice
Authors: Sridhar Arvind , Arif Pavel Mahmud , Ly Olivia T , Chen Hanna , Barney Miles , Gonzalez Francisco , Perike Srikanth , McCauley Mark , Rehman Jalees , Darbar Dawood
Published: June 2023

Introduction:
Diet induced obese (DIO) mice display increased inducible atrial fibrillation (AF) and an overall increase in reactive oxygen species (ROS) production. NADPH oxidase 2 (NOX2), a major source of cytosolic ROS production in human atria, has been implicated in AF independent of obesity and is significantly increased in the atria of DIO mice. Although treatment with MitoTEMPO, a mitochondrial specific antioxidant reduced AF burden in DIO mice, the actual role of NOX2 in increasing ROS production and atrial remodeling in the context of obesity-induced AF remains unclear.

Hypothesis:
To test the hypothesis that increased NOX2 modulates atrial remodeling in obesity-induced AF, we used control mice, DIO and
Nox2
-KO mice fed with a 60% HFD for 10 weeks (DIO-KO) and DIO mice treated with a NOX2 blocker, apocynin (DIO-Apocynin).

Methods:
Trans-esophageal rapid (TE) pacing was used to look at the AF phenotype. Cellular electrophysiology (EP), Western blotting, whole-cell patch clamping were performed to study ion channel remodeling and ROS production.

Results:
All three DIO mouse groups displayed significantly greater body weight compared to their respective controls (Figure A) After TE pacing, DIO-Apocynin mice displayed 28.26 ± 25.40 s and DIO-KO mice displayed 17.43 ± 31.80 s compared to 167.3 ± 168.9 s in DIO mice (Figure B). NOX2 inhibition reversed obesity-induced ion channel remodeling of potassium channels such as
KCNQ1
and
KCNE1
encoding for the IKs current and
KCNA5
encoding for the IKur current and also reduced mediators of oxidative stress. (Figure C-M) Lastly, voltage clamp in DIO-KO mice showed that NOX2 inhibition reverses obesity-induced IK current increase. (Figure N-O)

Conclusions:
Thus, these results prove that antioxidant therapy targeting Nox2 abrogated ion channel remodeling and reversed the obesity-induced AF burden. Our findings show the importance of targeting specific antioxidant pathways to manage the AF in patients with obesity.
Abstract 14513: An Aberrant Friend - Using Bundle Branch Block for Septal Accessory Pathway Localization
Authors: Sabzwari Syed Rafay Ali , Barrett Christopher , Mann James , CERBIN LUKASZ , Garg Lohit , Tumolo Alexis , Sandhu Amneet , Rosenberg Michael , Aleong Ryan G , Varosy Paul D , Zipse Matthew , Tzou Wendy , West John , Sanchez Jose
Published: June 2023

Introduction:
While changes in the ventriculoatrial (VA) time with RBBB or LBBB during ORT utilizing a free wall accessory pathway (AP) is well described, such a change in VA time can also be helpful in identifying the location of a septal AP.

Objectives:
To demonstrate the effect of RBBB and LBBB aberrancy on the VA time for ORT involving septal AP and thereby assist in identifying a posteroseptal AP.

Results:
A 51-year-old man with WPW syndrome was referred for EP study and ablation due to palpitations. With programmed atrial extrastimulation, an atypical echo beat was noted. While attempting to induce tachycardia, double atrial extrastimuli resulted in non-sustained ORT both with RBBB and LBBB aberrancies (Figure). Measurement of the VA time during non-sustained ORT demonstrated a VA time that was longer in the presence of LBBB aberrancy (110ms) than RBBB aberrancy (97ms) compared to narrow QRS (95ms). Electroanatomic mapping identified the earliest atrial activation of the echo beat on the right posteroseptum. Radiofrequency ablation at this site resulted in immediate loss of ventricular pre-excitation.

Conclusions:
Changes in the VA interval during AP-mediated SVT are especially important for pathway localization. As demonstrated in prior studies, for free wall APs, the difference between sinus and bundle branch block time (ΔVA) is usually >35ms compared to <35ms for septal APs. Furthermore, studies described that for septal APs, posteroseptal APs have a greater VA time with LBBB, anteroseptal APs with RBBB and no significant change in VA time with midseptal APs. By demonstrating both RBBB and LBBB aberrancy in this patient, this case uniquely validates the concept that the VA time with LBBB aberrancy is greater with posteroseptal APs.
Abstract 14531: Intracardiac versus Transvenous Pacemaker Implantation: Impact on Clinical Outcomes and Healthcare Utilization
Authors: Mararenko Anton , Udongwo Ndausung , Odak Mihir , Heaton Joseph , Pannu Viraaj , Douedi Steven , Alshami Abbas , Tavakolian Kameron , Asif Arif , mushtaq arman , Sealove Brett , Zacks Eran S
Published: June 2023

Introduction:
Permanent pacemakers are frequently used to treat disorders of cardiac rhythms. Recently, intracardiac (leadless) pacemakers offer potential treatment with an alternative insertion procedure due to their novel design. Literature comparing hospitalization outcomes between the devices is scarce. We aim to assess the impact of intracardiac pacemakers on readmissions and hospitalization trends.

Methods:
We analyzed the National Readmissions Database (NRD) from 2016 to 2019 seeking patients admitted for sick sinus syndrome, second-degree or third-degree AV block who received either a transvenous pacemaker or an intracardiac pacemaker. Patients were stratified by device type and assessed for 30-day readmissions, inpatient mortality, and length of stay. Descriptive statistics, Cox proportional hazards and multivariate regressions were used to compare the groups.

Results:
During the studied period, 21,782 patients met the inclusion criteria. Transvenous pacemakers were implanted in 17,677 patients and intracardiac pacemakers implanted in 4,017 patients. The mean age was 81.07 years, and 45.52% were female. No statistical difference was noted for readmissions (HR 1.14, 95% CI 0.92 - 1.41, p = 0.225) and inpatient mortality (HR 1.36, 95% CI 0.71 - 2.62, p = 0.352) between transvenous and intracardiac groups. Kaplan-Meier curves for readmission and mortality are presented in Figure 1A and 1B, respectively. Multivariate linear regression revealed that length of stay was 0.54 (95% CI 0.26 - 0.83, p < 0.001) days longer for intracardiac group.

Conclusion:
Hospitalization outcomes associated with intracardiac pacemakers are comparable to traditional transvenous pacemakers. Patients may benefit from the use of this new device without incurring additional resource utilization. Further studies are needed to compare long term outcomes between transvenous and intracardiac pacemakers.