bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12030: Myocardial Extracellular Volume in Patients With Type 2 Diabetes
Authors: Bojer Annemie S , Soerensen Martin Heyn , Gaede Peter , Madsen Per L
Published: June 2023

Introduction:
Myocardial interstitial fibrosis expands the extracellular volume (ECV) and is in patients with type 2 diabetes implicated in the development of heart failure. ECV can be determined with gadolinium-contrast magnetic resonance imaging.

Hypothesis:
We investigated if known risk factors for cardiovascular disease were associated with increased ECV in patients with type 2 diabetes.

Methods:
296 patients with type 2 diabetes and 21 healthy sex and age-matched controls were included in a cross-sectional magnetic resonance imaging study. The influence of risk factors on ECV was investigated by multiple regression analysis.

Results:
Controls and patients with type 2 diabetes without complications had similar ECV (27.1±2.1% vs. 27.9±2.6%, p=0.2). Compared to patients without, ECV was significantly increased in patients with 1≥ complication (29.0±3.3%, p=0.02). Both in univariable analysis and after multivariable adjustment, ischemic heart disease, autonomic neuropathy and active smoking were associated with increased levels of ECV. Active smoking exhibited the largest effect size (ß=2.0%-point 95%CI 0.7 to 3.3). Former smokers had similar ECV than never smokers. Albuminuria and systolic blood pressure were inversely associated with ECV in multivariable analysis but after adjustment for medication suspected to affect ECV the association to albuminuria was no longer significant (p=0.1). There was a trend toward SGLT2i treatment being associated with reduced ECV (-0.8% 95%CI -1.7 to 0.06, p=0.067).

Conclusions:
Patients with complications to diabetes have increased ECV not seen in patients without. Active but not former smoking was highly associated with increased ECV but also Ischemic heart disease, and autonomic neuropathy.
Abstract 12034: Diffuse Myocardial Fibrosis, Its Distribution And Relationship To Clinical Outcome And Ventricular Function In Single Ventricles Before And After Fontan: A Cardiac Magnetic Resonance Outcome Study
Authors: Joyce Jeremiah , Convery Michael , Donnelly Elizabeth , Jones Andrea , Giner Cassie , Biko David , Harris Matthew A , Partington Sara , Whitehead Kevin , Quartermain Michael D , Mercer-Rosa Laura M , Fogel Mark A
Published: June 2023

Introduction:
Patients with single ventricle (SV) anatomy are susceptible to myocardial fibrosis as measured by cardiac magnetic resonance (CMR) imaging. This study investigated the association of diffuse myocardial fibrosis prior to Fontan with ventricular function and clinical outcomes after Fontan completion.

Methods:
Retrospective cohort study of consecutive SV patients who underwent CMR T1 mapping prior to Fontan. Native T1 time and extracellular volume (ECV) of the dominant ventricle and a free wall region of interest (ROI) were measured on CMR pre-Fontan. Longitudinal strain was measured on echocardiography pre- and post-Fontan. Associations between pre-Fontan fibrosis, strain, and clinical outcomes were evaluated using linear and logistic regression.

Results:
40 patients were included (table 1). ECV directly correlated to the number of ICU days and post-Fontan strain. The coefficient of variation (CV) of ECV directly correlated to hospital and chest tube days. When limited to single right ventricles (RV), T1 directly correlated to strain pre-Fontan. ECV directly correlated to ICU days as well as strain pre- and post-Fontan. ECV ROI directly correlated to strain post-Fontan. The CV of ECV directly correlated to the number of hospital days (table 2).

Conclusions:
Myocardial fibrosis prior to Fontan may portend the clinical course after Fontan and should be considered for risk stratification. The CV of ECV is a novel measure of diffuse fibrosis that is associated with clinical outcome. For single RV patients, fibrosis before Fontan is associated with worse ventricular function after. The use of reverse remodeling agents prior to Fontan should be considered.
Abstract 12035: Cardiotoxicity-Based Model for Assessment of Drug Value in Breast Cancer
Authors: Oren Ohad , Bhatt Deepak L
Published: June 2023

Introduction:
Cardiovascular toxicity mediated by chemotherapy drugs has important implications on the clinical outcomes of patients with breast cancer. We created a multi-component drug value framework incorporating efficacy, safety, cost, and cardiovascular toxicity data to define the overall value of standard regimens. The impact of heart failure incidence on the value score of each regimen was evaluated.

Methods:
The NCCN guidelines were reviewed, and four standard chemotherapy regimens used in non-metastatic HER-2 negative breast cancer were selected. PubMed was reviewed for randomized clinical trials establishing the role of each regimen. Data on the efficacy (defined as 5-year survival) and toxicity (defined as incidence of the most frequent grade 3 toxicity) profile of each regimen were extracted. Data on regimen-specific heart failure incidence at follow up were collected from prospective studies. Regimen-specific costs were derived from a recent observational cohort study. Total drug value scores (range 2.2-8.6, traditional, 2.9-11.7 upgraded) were computed and the effect of cardiotoxicity data on drug value scores was evaluated.

Results:
Anthracycline-containing regimens had lower mean drug value scores than anthracycline-free regimens (5.3, 61.6% versus 7.4, 86.0%) using a traditional value system based on efficacy, safety, and cost. When data on heart failure incidence were incorporated into the value assessment, anthracycline-containing regimens had lower relative value scores (mean decrease 10.7%) while anthracycline-free combinations had higher relative scores (mean increase 4.3%), compared with a traditional model. Regimen-specific value scores were modified by the addition of heart failure data. Drug value assessments that included efficacy, safety and cost showed superiority of docetaxel, adriamycin, cyclophosphamide (TAC) relative to cyclophosphamide, methotrexate, fluorouracil (CMF) (7.1, 82.6%, 6.6, 76.7%) and the addition of heart failure incidence data reversed that trend (8.6, 73.5%, 9.6, 82.0%).

Conclusions:
Inclusion of cardiovascular toxicity data modifies the value scores of standard chemotherapy regimens used in breast cancer and likely provides a more patient-centric value assessment.
Abstract 12043: The Genetic Variant P.(Lys3344Glu) in
APOB
Causes Familial Hypercholesterolemia
Authors: Cenarro Ana , Galicia-Garcia Unai , Marco-Benedi Victoria , BEA ANA M , Martin Cesar , Civeira Fernando
Published: June 2023

Introduction:
Genetic variation in the
APOB
gene is frequent but the pathogenicity of most of the variations is unknown. Only the variant in APOB p.(Arg3527Gln), known as familial defective apoB100, unequivocally produces familial hypercholesterolemia (FH).

Hypothesis:
A new variant in
APOB
responsible for HF in three unrelated Spanish families is presented. Its pathogenesis has been demonstrated by family segregation and apoB-LDL receptor binding analysis.

Methods:
The three probands correspond to two women and one man referred for study of their hypercholesterolemia at the Lipid Unit of the Miguel Servet Hospital in Zaragoza, Spain. Secondary causes were ruled out and family history showed a dominant segregation of hypercholesterolemia in their families. Their clinical characteristics are described in the table.

Results:
Sequencing analysis of the
LDLR, APOB, PCSK9
, and
APOE
genes showed the c.10030A>G; p.(Lys3344Glu) variant. No other pathogenic mutations were found.The family study included 14 first-degree relatives, with 8 of them being carriers of the
APOB
variant with a mean age of 42.5 years. The mean (range) of LDLc was 309 mg/dL (254-419) in carriers and 147 (98-179) in unaffected relatives. The apoB-LDL receptor binding study of the serum of the 3 probands (EC50) showed a reduction equivalent to that obtained with apoB p.(Arg3527Gln), and approximately 50% lower than that obtained in control serum.

Conclusions:
The p.(Lys3344Glu) variant in
APOB
is causal for FH and its mechanism is a defect in the affinity of the defective protein for the LDL receptor.
Abstract 12045: Mapping the CaV1.2 Interactome in Rat Heart in vivo
Authors: Kushner Jared S. , Rodriques Aaron , Zakharov Sergey , Katchman Alexander , FANOURAKIS STAVROS , Marx Steven
Published: June 2023

Introduction:
The Ca2+ channel CaV1.2 is an essential part of excitation contraction coupling, neurotransmission and vascular tone. Identifying protein partners of CaV1.2 is critical to make mechanistic insights into these fundamental processes. Prior CaV1.2 proximity proteomes used APEX labeling, which labels other amino acids, introduces oxidative stress and is catalyzed ex vivo.

Hypothesis: α1C-TurboID knockin rats can generate tissue specific interactomes in vivo, in cells with intact cell and matrix contacts, which may differ substantially from interactomes made from ex vivo peroxidase catalyzed labeling.

Methods:
CRISPR/Cas9 homology directed repair (HDR) was applied to rat spermatogonial stem cells with a targeting vector that includes cacna1c exon 44, coding the C-terminus of CaV1.2, and birA*, which codes TurboID, cloned 3’ to the stop codon (Fig A). Figures were made with Biorender.

Results:
Streptavidin blotting of brain and heart lysates demonstrated robust biotinylation in knockin rats (Fig B). In paced heart myocytes, α1C-TurboID produces Ca2+ transients and responds appropriately to adrenergic stimulation (Fig C), indicating proper localization to the sarcolemma. Expression of α1C-TurboID does not alter systolic function (Fig D). Mass spectrometry of heart lysates affinity purified on streptavidin beads identified 629 proteins, of which 454 were significantly enriched in knockin rats. These include known sarcolemmal proteins and interactors of CaV1.2 (Fig E), which was confirmed by antibody detection (Fig F). 73% of these 454 proteins were not significantly enriched in the APEX-α1C proteome.

Conclusion:
TurboID fusion to CaV1.2 generates a reliable and substantially different proteome compared to other techniques. Successful in vivo characterization of the channel interactome confirms α1C-TurboID rats will be a powerful tool for identifying changing protein networks across developmental stages, tissues, and disease models.
Abstract 12050: Ketone Ester Supplementation Reduces Cardiac Inflammation and Enhances Cardiac Energetics in Acute Myocardial Infarction
Authors: Yurista Salva , Welsh Aidan , Jiang William , Eder Robert , Chen Shi , Foster Anna , Coll-Font Jaume , Rosenzweig Anthony , Nguyen Christopher T
Published: June 2023

Introduction:
Myocardial infarction (MI) is a major risk factor for the development of heart failure with reduce ejection fraction (HFrEF). While previous studies have focused on HFrEF, the role of ketone bodies in MI is unclear.

Hypothesis: K
etone may exert some cardioprotective effects following MI.

Methods:
Male Yorkshire pigs underwent percutaneous balloon occlusion of the LAD for 80 minutes followed by 72 hours reperfusion period. Oral ketone ester (BHB-butanediol monoester, KE, 550 mg/kg) or vehicle was administered during reperfusion and continued during the follow-up period. Simultaneous blood sampling from coronary sinus and artery was obtained to quantify the extraction fraction of major cardiac substrates. Scar size was measured by LGE CMR and molecular markers were assessed in the LV. The study was approved by the IACUC at the Massachusetts General Hospital.

Results:
KE induced ketosis within 30 min after ingestion. KE increased β-hydroxybutyrate (βOHB) extraction in healthy swine without affecting glucose and fatty acid (FA) consumption. Despite similar infarct size in both MI and MI-KE groups, cardiac expression of proinflammatory cytokines TNF-⍺, IL-1, IL-6, and cardiac injury TTNI3 alongside with plasma hs-cTnI were reduced by KE. The untreated MI hearts consumed less FA with no changes in glucose uptake, whereas hearts from KE-treated animals consumed more βOHB and FA. KE increased cardiac expression of genes involved in ketone utilization MCT1 and SCOT after MI (p<0.05 for all), indicating that cardiac uptake and utilization of βOHB as fuel were augmented. Together these metabolic changes were associated with an increase in cardiac ATP production. RNA-seq analysis identified differentially expressed genes related to mitochondrial energy metabolism.

Conclusions:
Oral KE induced ketosis and enhanced cardiac βOHB extraction in both healthy and infarcted hearts. Although infarct size was unchanged 72h after MI, acute oral supplementation with KE supressed cardiac inflammation and injury, altered cardiac substrate uptake and enhanced cardiac energetics following acute MI. Evaluating the potential chronic benefits of these changes on long-term remodeling after MI will be an exciting direction for future studies.
Abstract 12052: Multimarker Approach for Risk Stratification in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Hecht Sebastien , Giuliani Carlos M , Bernard Jeremy , Tastet Lionel , Abu-Alhayja'a Rami , Beaudoin Jonathan , Cote Nancy , De Larochelliere Robert , Dumont Eric , Kalavrouziotis Dimitri , Mohammadi Siamak , OConnor Kim , bernier mathieu , Paradis Jean-Michel , Clavel Marie-Annick A , Rodes-Cabau Josep , Pibarot Philippe
Published: June 2023

Introduction:
Transcatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement for the treatment of severe aortic stenosis (AS). However, TAVI may be futile in a substantial proportion of patients. The development of a blood multimarker approach encompassing cardiac damage, inflammation, cancer, and renal function could be useful to accurately identify patients who may benefit from TAVI versus those who may not.

Hypothesis:
the objective of this study was to examine the association between blood biomarkers and all-cause mortality following TAVI.

Methods:
Three hundred and sixty-three patients who underwent TAVI at our institution were prospectively recruited. Clinical and echocardiographic data were collected. Nine biomarkers were measured from blood samples collected before TAVI. The cohort was divided in 3 groups according to the number of elevated biomarkers (i.e ≥median of the cohort) per patients. Multivariable survival analysis was performed to evaluate the association between biomarkers and all-cause mortality. The incremental prognostic value of the biomarkers model to predict all-cause mortality was assessed using the net reclassification index (NRI).

Results:
In comparison with patients with 0-3 elevated biomarkers, those with 4-7 and 8-9 were older, had more comorbidities and higher rate of NYHA ≥III. They also had longer hospital stay following TAVI. During a median follow-up of 2.5 (1.9-3.2) years, 99 (27%) patients died. Using multivariable Cox analysis and patients with 0-3 elevated biomarkers as the referent group, those with 4-7 and 8-9 elevated biomarkers had a higher risk of all-cause mortality (HR [95%CI]: 1.83 [1.01-3.38], p=0.05, and HR [95%CI]: 4.09 [2.16-7.76], p<0.001, respectively). The addition of the number of elevated blood biomarkers provided important incremental prognostic value in comparison with the clinical model (NRI=0.71, p<0.001).

Conclusions:
An increasing number of elevated biomarkers was associated with higher risk of mortality after adjustment for baseline differences. Moreover, the biomarker model provided important incremental prognostic value beyond the clinical variables and could thus enhance risk stratification of patients undergoing TAVI.
Abstract 12053: Worsening Tricuspid Regurgitation After Leadless Pacemaker Implantation Leads to Higher Hospitalization for Heart Failure
Authors: Lee Kevin , Metzl Mark
Published: June 2023

Introduction:
One of the many purported benefits of a leadless pacemaker (LP) is avoidance of interaction with the tricuspid valve, decreasing tricuspid valve dysfunction from chronic injury resulting from contact with transvenous leads. Data suggests that 31-38% of patients develop worsening tricuspid regurgitation (TR) after transvenous pacemaker implantation. However, some recent data suggest that LP therapy is also associated with a higher incidence of worsening TR, possibly similar to transvenous pacemakers. We present data from a large community-based health system on the incidence of worsening TR after LP implantation and its clinical implications.

Methods:
A total of 256 patients (mean age 80±10 years, 61% male) who received Micra leadless single chamber pacemaker devices at the NorthShore University HealthSystem between April 2017 and November 2021 were retrospectively reviewed. A total of 103 patients (40%) received both a transthoracic echocardiogram within 6 months pre-implantation and 6 months post-implantation. Characterization of TR and heart failure hospitalization were gathered through chart review.

Results:
Of the 103 patients, 39 (38%) were found to have worsening of their TR after LP implantation when compared to before. Of the patients with worsening TR, 18 (46%) required hospitalization for heart failure within 12 months, compared to 15 (23%) without worsening TR (
X
2
= 5.7,
p
= 0.02).

Conclusions:
LP implantation is associated with comparable levels of worsening TR (38%) when compared to transvenous pacemakers. Worsening TR is associated with increased heart failure hospitalization within 12 months. More data is required to establish the reasoning behind the comparable levels of worsening TR in LP given the lack of mechanical interaction with the tricuspid valve apparatus.
Abstract 12058: The Impact of Cardiovascular Health Intervention on Plasma Metabolomic Profiles
Authors: Beydoun Nour , Liu Chang , Islam Shabatun , Rooney Kimberly , Taylor Herman A , Jones Dean , Igho-Pemu Priscilla E , Quyyumi Arshed A , Searles Charles D
Published: June 2023

Introduction:
Previously, we used plasma metabolomics profiling to identify metabolites underlying cardiovascular health (CVH) in participants of the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity Study. Herein, we explored whether a health intervention could alter plasma concentrations of metabolites associated with CVH in MECA participants with poor CVH.

Methods:
71 Black adults without known cardiovascular disease and with poor CVH, defined as AHA Life’s Simple 7 (LS7) score <8, were given a technology-enabled behavioral intervention platform (Health360x) for 6 months with or without access to a health coach. Metabolites were assessed pre- and post-intervention by untargeted high-resolution metabolomics profiling. Metabolome wide association study (MWAS) was conducted to identify differentially expressed metabolites and Mummichog was used to identify metabolic pathways that were differentially enriched after the intervention. Annotations were performed by matching to an in-house library of confirmed metabolites. Paired t-test and Wilcoxon signed-rank test were used to compare clinical metrics.

Results:
Mean age was 55
+
9.0 years, 69% female. Total LS7 scores improved from 6.2 (
+
1.49) to 6.5 (
+
1.74) with the intervention. While total and subcomponent LS7 scores and clinical metrics (BMI, blood pressure, glucose and cholesterol levels) trended toward improvement, the changes were not statistically significant. MWAS identified 18 metabolites that were significantly changed after intervention, including glutamine and glutamate. Pathway analysis demonstrated 30 metabolic pathways that were significantly changed with intervention, including glutamate, aspartate, asparagine, arginine and proline metabolism.

Conclusions:
Six-months of lifestyle intervention altered activity of 30 metabolic pathways without significant alterations in the clinical metrics. These metabolites and pathways appear to be indicators of a healthier lifestyle in the Black population, potentially supporting their use as markers of CVH and possible therapeutic targets.
Abstract 12067: The Impact of the COVID-19 Pandemic on Congenital Heart Defect-Related Healthcare by Age and Insurance Status
Authors: Farr Sherry L , ROSE CHARLES , Downing Karrie F , Fundora Michael , Oster Matthew E
Published: June 2023

Objective:
To examine congenital heart defect (CHD)-related healthcare for children and adults during the COVID-19 pandemic.

Methods:
IBM Marketscan® Commercial and Multi-State Medicaid Databases from 2018-2020 were used to examine outpatient and inpatient encounters and cardiac procedures/surgeries with ≥ 1 CHD ICD-10-CM codes (Q20-Q26; Z87.74), excluding isolated Q21.1 and encounters with a COVID-19 ICD-10-CM code. Monthly rates of encounter types per 5 mil enrolled children and 15 mil enrolled adults and percent telemedicine encounters were averaged across 2018-2019 and compared to 2020 by age (0-17y and 18-64y) using chi square tests.

Results:
Data included 583,069 commercial (private) and 796,579 Medicaid CHD-related encounters in 2018-2020. For all groups, rates of encounters were lowest in Mar-May 2020 (Fig). In Jun-Dec 2020, rates returned approximately to 2018-19 levels, but were lower than needed to offset fewer encounters in the spring. Per 5 mil enrolled children in private and public insurance, there were over 8,400 fewer CHD-related outpatient encounters, 5,300 fewer inpatient encounters, and 260 fewer cardiac procedures/surgeries in 2020 compared to 2018-19 (p<0.0001). In Jan-Feb 2020, adult Medicaid outpatient encounters were above 2018-19 levels. However, per 15 mil enrolled privately- and publicly-insured adults, there were over 5,600 fewer inpatient encounters and 460 fewer cardiac procedures/surgeries in 2020 compared to 2018-19. Telemedicine encounters were highest in Apr 2020 and remained above 2018-19 levels through Dec 2020, with the highest percentage among privately-insured adults (p<0.0001).

Conclusion:
In the second half of 2020, CHD-related encounters returned to 2018-19 levels, yet did not compensate for lower-than-expected encounters in the spring, resulting in fewer pediatric CHD-related encounters and fewer adult CHD-related inpatient encounters in 2020. Use of telemedicine differed by insurance and age.
Abstract 12072: EKG Appearance and Evolution of Baseline EKG-Characteristics in the Worldwide First Genetically Modified Porcine-to-Human Xenotransplant (“Pig Heart-in-Human Body”)
Authors: Kagan Calvin , Amara Richard S , Haq Muhammad , Mohiuddin Muhammad , Hong-Zohlman Susie N , Ananthram Manjula , Hong Charles C , See Vincent Y , Shorofsky Stephen , Griffith Bartley , Dickfeld Timm
Published: June 2023

Introduction:
The worldwide first genetically modified porcine-to-human cardiac xenotransplantation was performed in January 2022 at the University of Maryland with the recipient surviving for 61 days.

Methods:
Daily 12- lead ECGs were obtained during the post-operative period.

Results:
Accepted “pig heart-in-pig body” ECG parameters demonstrate a short PR interval (50-120ms), short QRS (70-90ms) and short QT (260-380ms). However, the first-ever EKG of a genetically modified heart xenotransplant (“pig heart-in-human body”) demonstrated a relatively longer PR interval of 190ms, QRS duration of 138ms and QT of 538ms (in setting of sinus bradycardia, interventricular conduction delay and inferior/antero-lateral T wave inversions; Figure 1).

Prolonged intrinsic PR intervals remained stable during the post-operative course with 210±22ms [range 142-246ms]. However, atrial pacing demonstrated evidence of decremental intra-atrial conduction delay/AV-conduction delay most pronounced on day 12 (PR: 380ms). QRS duration remained prolonged with 145±16ms [range 116-192ms] but shortened during the post-operative course (day 21-40 vs 41-60: 148±14ms vs 132±11ms; p<0.001). Increased QT persisted with 509±54ms [range 384-650ms] with dynamic fluctuations (QT nadir around day 14 (428±22ms vs 533±36ms; p<0.001).

Conclusions:
ECG parameters of the first genetically modified porcine-to-human cardiac xenotransplant (“pig heart-in-human body”) demonstrated prolongation over the usually encountered ECG measurements in the donor (“pig heart- in-pig body”) including changes in cardiac depolarization and repolarization. Prolonged ECG parameters persisted but showed dynamic changes during post-operative period. This provides a first insight into the novel and evolving field of xenotransplanation suggesting a complex interplay of inter-species physiology and porcine denervation in addition to post-surgical and medication-related changes.
Abstract 12075: Extracellular Vesicle Cargo Long-Noncoding RNAs Are Dynamic Biomarkers in Acute Decompensated Heart Failure
Authors: Gokulnath Priyanka , Lehmann H Immo , Spanos Michail , Sheng Quanhu , Rodosthenous Rodosthenis , Chatterjee Emeli , Hutchins Elizabeth , Li Guoping , Wang Ashley Mingyi , Van Keuren-Jensen kendall , Shah Ravi V , Das Saumya
Published: June 2023

Introduction:
Acute decompensation is associated with increased long-term mortality in patients with heart failure (HF). Biomarkers of acute HF that are dynamic during decongestion may provide physiologic insight for this observation. We hypothesized that long-noncoding RNAs (lncRNAs) and mRNAs in extracellular vesicles (EVs) not only mark different types of HF, but also may be dynamically altered with decongestion across physiologically important pathways.

Methods:
RNA sequencing was performed on plasma-derived EVs in acute HF patients (7 HFpEF; 7 HFrEF) at hospital admission (V1) and at discharge (V2) along with 9 controls without HF. Differential expression analysis was performed using DESeq2 across groups and time-points. Transcripts were prioritized by fold change (±1.5) and statistical significance (<5% FDR). We subsequently validated targets in EVs from 182 additional patients (24 control; 86 HFpEF; 72 HFrEF).

Results:
Between HF and control patients, 138 lncRNAs and 147 mRNAs were different (Fig a,b). LncRNAs were confirmed to be exclusively present in EVs. Of 13 targets investigated in our validation cohort, 5 lncRNAs and 6 mRNAs were significantly different between control and HF (age, sex-adjusted; Fig c). Pairwise comparisons between EV RNAs at hospital admission versus decongestion revealed a significant change in 4 lncRNAs (Fig d,e ) that was independent of weight change during hospitalization. Notably, distinct fragments derived from these transcripts were noted in HF versus control groups.

Conclusions:
The plasma EV transcriptome is significantly altered in patients with acute HF. Plasma EV-derived lncRNA fragments demarcate congestion and decongestion better than mRNAs, may be markers for pathophysiologically relevant pathways independent of volume status, and may provide additional prognostic information.
Abstract 12099: Relationship Between Fatigue Subtype and Heart Failure Admission, Quality of Life, and Mortality in Persons With Heart Failure: A Secondary Analysis of the Atherosclerosis Risk in Communities Study
Authors: Pavlovic Noelle , Leoutsakos Jeannie-Marie , Abshire Martha , Dennison Himmelfarb Cheryl R , Szanton Sarah , Ndumele Chiadi E
Published: June 2023

Introduction
Fatigue is one of the most common and distressing symptoms of heart failure (HF). It consists of two types: general and exertional. Although it’s common, little is known about whether and which type of fatigue is associated with patient reported and clinical outcomes. We conducted a secondary data analysis of the Atherosclerosis Risk in Communities (ARIC) study to determine if fatigue type predicts key patient reported and clinical outcomes in persons with HF.

Methods
This analysis included 1,068 individuals with a diagnosis of prevalent HF at visit 5 (2011-2013) of the ARIC study with available survey data on general and exertional fatigue. Four fatigue subtypes were identified previously through latent class analysis on general and exertional fatigue survey items in this sample. These fatigue subtypes are: 1) High general & exertional, 2) High general & low exertional, 3) Moderate general & exertional, and 4) Low/No fatigue (reference category). To assess the relationship between fatigue subtype and outcomes, we used latent class regression, regressing HF hospitalization, quality of life (QOL, SF-12 scale) and mortality on fatigue subtype, adjusting for covariates (demographics, clinical comorbidities, and medications).

Results
Our sample was 54% female and 38% Black, with a mean age of 77 ± 5.5. Those with the high general & exertional fatigue subtype had 2.2 times higher likelihood of HF hospitalization than those with the low/no fatigue subtype (OR = 2.2; 95%CI = 1.2, 4.1). Those with the high general & exertional fatigue subtype had significantly poorer mean physical (50.3 v 64.6, p<0.001) and mental (49.3 v 58.0, p<0.001) QOL than those with the low/no fatigue subtype. Those with the moderate general & exertional fatigue subtype also had significantly poorer physical QOL than the low/no fatigue subtype (61.9 v 64.6, p<0.001). There were no significant differences in mortality between fatigue subtypes.

Conclusions
Fatigue subtype in persons with HF is associated with HF admissions and quality of life. It will be important to elucidate the pathways underlying the development of fatigue and to determine whether targeting fatigue can improve clinical outcomes.
Abstract 12107: Short-Term and De-Escalation Dual Antiplatelet Therapy for Patients With Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis
Authors: Kuno Toshiki , Watanabe Atsuyuki , Shoji Satoshi , Fujisaki Tomohiro , Takagi Hisato , Deharo Pierre , Cuisset Thomas , Kohsaka Shun , Bhatt Deepak L
Published: June 2023

Background:
Short-term (<6 month) or de-escalation (e.g. switching potent P2Y
12
inhibitors to less potent/lower-dose agents a month after the event) dual antiplatelet therapy (DAPT) have become an attractive therapeutic strategy for patients with acute coronary syndrome (ACS). However, these strategies have never been randomly compared.

Methods:
PubMed, EMBASE, and Cochrane Central were searched in April 2022. Randomized controlled trials (RCTs) or their subgroup analyses that included ACS patients, with standard (12 months), extended (≥18 months), short-term and unguided de-escalation DAPT strategy, along with the guided DAPT strategy with genotype or platelet function tests were identified. The efficacy outcome (major adverse cardiovascular events: MACE) was defined as a composite of cardiovascular death, myocardial infarction, or stroke. The safety outcomes were mainly defined as major or minor bleeding, and major bleeding.

Results:
This network meta-analysis included 32 RCTs with 103,497 patients. While there was no significant difference in efficacy among the short DAPT, unguided de-escalation and guided-selection strategy, the unguided de-escalation strategy alone was associated with reduced risks of MACE compared with standard DAPT (e.g. versus DAPT with clopidogrel; HR [95% CI]: 0.66 [0.48-0.91]). Both the short DAPT and de-escalation strategies were associated with reduced risks of major or minor bleeding compared with other strategies including the guided-selection (HR [95% CI]: 0.66 [0.47-0.93], 0.48 [0.33-0.71], respectively); the short DAPT strategy alone was associated with a reduced risk of major bleeding compared with standard, extended and guided-selection DAPT (HR [95%CI]: 0.55 [0.33-0.92]).

Conclusions:
In ACS patients, the unguided de-escalation strategy was associated with reduced risks of MACE, while the short DAPT strategy was associated with decreased rates of major bleeding compared with standard DAPT, suggesting both strategies can be used in select patients by balancing patients’ ischemic and bleeding risks.
Abstract 12125: Ambulatory Pulmonary Artery Pressure-Guided Therapy in Patients With Chronic Heart Failure: A Systematic Review and Meta-Analysis
Authors: Trongtorsak Angkawipa , Thangjui Sittinun , Dunleavy Michael , Luo Shengyuan , Osman Heba , Chau Vinh , Marinescu Karolina , Rao Anupama , Volgman Annabelle , suboc tisha
Published: June 2023

Background:
In the past year, an implantable pulmonary artery pressure (PAP) sensor with CardioMEMS was approved by the FDA for heart failure (HF) patients with New York Heart Association (NYHA) class III or those with HF-related hospitalization (HFH). However, recent guidelines have not strongly recommended adding the PAP sensor to the standard of care in chronic HF patients.
Objectives:
We conducted this systematic review and meta-analysis to evaluate whether remote PAP-guided therapy can improve outcomes in chronic HF patients.

Methods:
We searched MEDLINE and Embase databases from inception to May 2022 to identify studies that compared outcomes of interest, including HFH and all-cause mortality in patients with HF who received remote PAP sensors in addition to the standard of care and those with the standard of care alone. Data from each study were combined using the random-effects model.

Results:
Four studies (2 randomized controlled trials and 2 matched cohort studies) with 7,505 patients (3,693 in the PAP sensor group and 3,812 in the control group) were included. The use of implantable PAP sensors in patients with chronic HF was associated with significantly lower HFH (hazard ratio (HR) = 0.76, 95% conference interval (CI) 0.68-0.84, p<0.001) and all-cause mortality (HR=0.73, 95%CI 0.62-0.85, p<0.001) as shown in Figure 1.

Conclusions:
Our meta-analysis demonstrated a significant reduction in HFH and mortality in HF patients with NYHA class III and remote PAP-guided therapy. Adding an ambulatory PAP sensor to the standard care may improve outcomes in chronic HF patients with NYHA class III.
Abstract 12126: Trends in Lipoprotein(a) Testing in Individuals With Cardiovascular Disease
Authors: Bhatia Harpreet S , Desai Paresh , Zhu Wenhong , Tsimikas Sotirios , Yeang Calvin
Published: June 2023

Introduction:
There is consensus amongst major international societal guidelines including the AHA/ACC that elevated lipoprotein(a) [Lp(a)] > 50 mg/dL, present in 20% of the population, is a likely causal, independent, and hereditary risk factor for several cardiovascular (CVD) conditions. Despite its high prevalence, clinical measurement of Lp(a) has anecdotally been considered rare but has not been systematically quantified.

Methods:
We assessed the prevalence of Lp(a) testing for various CVD conditions across six academic medical centers associated with the University of California (UC), in total and by year from 2012-2021. Data from the UC data warehouse on unique CVD diagnoses using ICD codes, and unique Lp(a) testing for individuals with each diagnosis were collected. The proportion of individuals with a given CVD diagnosis and Lp(a) testing at any time during the study period or in the same year of their diagnosis was quantified. Finally, we evaluated the prevalence of elevated Lp(a) (>30 mg/dL and >50 mg/dL) for each diagnosis.

Results:
From 2012-2021, there were 18,830 unique Lp(a) tests. Lp(a) testing was performed in 6,855 individuals with ischemic heart disease (3.1%), 2,454 (3.4%) with MI, 1,157 (2.1%) with PVD, 1,261 (3.4%) with carotid stenosis, 1,250 (1.8%) with stroke, 908 (3.4%) with aortic stenosis, and 5,136 (3.6%) with a family history of CVD. For most conditions, the prevalence of testing in the same year as the diagnosis of CVD was relatively consistent over the study period, except for a progressive increase among those with MI (
Figure
). Across CVD diagnoses, the prevalence of Lp(a) >30mg/dL was 47.9 to 55.3% and for Lp(a) >50 mg/dL was 36.7 to 44.9%. The highest prevalence of elevated Lp(a) was among those with carotid stenosis, and the lowest was among those with family history of CVD.

Conclusions:
Lp(a) testing persists at low rates, even among those with diagnosed CVD, and remained stable over the study period except for MI.
Abstract 12149: Assessment of Cryoballoon Occlusion Shift From the Pulmonary Vein Ostium Following Freeze Initiation Using a Dielectric Imaging System
Authors: Tomaiko-Clark Emrie D , Weiss J Peter , Zawaneh Michael , Su Wilber
Published: June 2023

Introduction:
Cryoballoon ablation for atrial fibrillation (AF) has been widely adopted clinically. However, dislodgement from the pulmonary vein (PV) ostium following freeze initiation commonly occurs due to a sudden rise in balloon pressure, known as the “pop-out” phenomenon. This can often only be partially detected using continuous color Doppler or repeat angiography after the initiation of freeze. We aim to access the incidence of this phenomenon using the dielectric imaging system in comparison to intracardiac echocardiography (ICE).

Methods:
Ten patients underwent de novo cryoballoon ablation for paroxysmal or persistent AF with the use of the KODEX-EPD dielectric imaging system (Philips, Amsterdam, Netherlands). A baseline assessment and injection were performed pre-ablation followed by analysis of occulsion via the KODEX Occlusion Viewer. Simultaneous assessment was performed by the operator utilizing ICE. Repeat assessment with injection was performed after ablation start to assess whether the cryoballoon remained occluded on ICE and by KODEX’s occlusion assessment.

Results:
There was a high correlation between KODEX and ICE for assessment of balloon occlusion prior to ablation (91.7±23.6%). KODEX demonstrated an overall sensitivity (88.6%), specificity (75.0%), positive predictive value (76.5%), and negative predictive value (87.8%) of the occlusion tool validated by ICE. Both imaging modalities detected a leak after initial full occlusion, an incidence of 24.3% on Kodex and 23.8% on ICE.

Conclusions:
Balloon contact with the PV is vital for an effective, transmural lesion. The dielectric imaging system and ICE confirmed high incidence of this “pop-out” phenomenon, which can lead to incomplete PV isolation. The KODEX-EPD occlusion tool is highly sensitive and specific to assist in the identification of this phenomenon and may improve the outcome for cryoballoon procedures. In the future a more compliant cryoballoon design, without a shift in balloon pressure during ablation, may avoid this phenomenon.
Abstract 12150: Acute Type B Aortic Dissection a 15-Year, Single-Center Experience
Authors: Serna-Gallegos Derek R , Dai Yancheng , Brown James , Aranda-Michel Edgar , Bianco Valentino , Yousef Sarah , Sultan Ibrahim
Published: June 2023

Introduction:
Treatment of acute type B aortic dissection (ATBAD) has evolved with the use of endovascular technology. This study evaluates the short and long-term outcomes of patients with ATBAD over a 15-year period.

Methods:
A retrospective review identified patients with ATBAD at our institution between 2006 and 2020. Patients were analyzed based on presentation status (complicated vs. uncomplicated) and treatment. Complicated ATBAD (cATBAD) included malperfusion of any vascular bed, intractable pain, rupture, or rapid expansion. Postoperative outcomes were evaluated within the initial 30 days after diagnosis when managed medically or within thirty days of surgical intervention. Descriptive statistics was performed to assess short-term outcomes. Kaplan-Meier survival was performed to assess long-term mortality.

Results:
A total of 296 patients presented with ATBAD in the study period. Out of those, 121 patients presented with cATBAD, while 175 patients presented with uncomplicated ATBAD (uATBAD). Out of the cATBAD group, 89 were treated with TEVAR, and 32 were treated with medication only. The cATBAD group was younger than the uCTBAD group (62.0 vs. 65.2, p=0.05). Early mortality was more common in cATBAD than uATBAD (9.9% vs 2.3%, p=0.013).

When comparing cATBAD who underwent TEVAR vs conservative medical management, early mortality was higher in the medication only group (12.5% vs 9.0% p = 0.013). Permanent paraplegia occurred in 1.1% (1/89)of patients undergoing TEVAR. Kaplan-Meier survival analysis demonstrated no significant difference in long-term mortality between the cATBAD and uATBAD groups (Logrank p = 0.23). Among the uATBAD patients, 10.3% (18/175) required future intervention for type B dissection (12 TEVAR, 6 open). Among the TEVAR patients, 20.2% (18/89) required re-operations (11 endovascular repairs, 7 open).

Conclusions:
ATBAD is associated with significant morbidity and mortality, especially in the setting of a complicated presentation. While uATBAD is associated with better short-term outcomes, the diminishing difference in long-term outcome between cATBAD and uATBAD calls for reevaluation of our indications for intervention and may suggest that the remodeling associated with TEVAR could have long term benefit.
Abstract 12156: Small Proline-Rich Repeat Protein 1a is a Significant Functional Target of Microrna-150 in Mouse Hearts and Human Cardiac Fibroblasts
Authors: Kawaguchi Satoshi , Moukette Bruno , Sepulveda Marisa , Kim Il-man
Published: June 2023

Background and Aims:
Cardiac injury induces dynamic changes in the expression of microRNAs (miRs). MiR-150 is conserved between rodents and humans, and its downregulation is markedly associated with heart failure (HF) severity and outcome in humans. Using systemic and cardiomyocyte (CM)-specific knockout (KO) mouse models, we reported that miR-150 plays a cardioprotective role in part by decreasing CM apoptosis, and that pro-apoptotic small proline-rich protein 1a (
Sprr1a
) is a direct and functional target of miR-150 in CMs. We also showed that
Sprr1a
knockdown in mice improves cardiac dysfunction and fibrosis post-myocardial infarction (MI), and that
Sprr1a
is upregulated in mouse cardiac fibroblasts (CFs) isolated from ischemic myocardium. However, the direct functional relationship between miR-150 and SPRR1A in MI and human CF (HCF) activation has never been established.

Methods & Results:
Here, we demonstrate using a novel miR-150 KO;
Sprr1a
-hypomorphic (

Sprr1a
hypo/hypo

) mouse model that
Sprr1a
knockdown blunts cardiac dysfunction, damage, inflammation, apoptosis and fibrosis post-MI caused by miR-150 loss. MiR-150 KO;

Sprr1a
hypo/hypo

mice also exhibit decreased pro-fibrotic markers in the infarct areas of hearts as compared to miR-150 KO mice. Our primary adult HCF studies further reveal that
SPRR1A
is upregulated in HCFs subjected to simulated ischemia/reperfusion, while its expression is downregulated in HCFs by a cardioprotective β-blocker carvedilol, which is inversely associated with miR-150 expression. MiR-150 knockdown in HCFs also increases pro-fibrotic
SPRR1A
. Lastly, protective roles of miR-150 in HCFs are in part mediated by the functional repression of
SPRR1A
(See Figure).

Conclusions:
Our findings delineate a pivotal functional interaction between miR-150 and
Sprr1a
as a novel regulatory mechanism pertinent to CF activation post-MI. This axis could be a therapeutic target for intervention in ischemic HF and cardiac fibrosis.
Abstract 12158: Left Atrial Volumes and Strain by Cardiac Magnetic Resonance Are Associated With Long Term Outcomes in Patients With Hypertrophic Cardiomyopathy
Authors: Khalil Maria , Benjamin Mina M , Munir Muhammad S , Kinno Menhel , Syed Mushabbar
Published: June 2023

Introduction:
We sought to evaluate left atrial (LA) morphology, function and strain by cardiac magnetic resonance (CMR) in hypertrophic cardiomyopathy (HCM) patients and the association of these parameters with long-term clinical outcomes.

Methods:
We retrospectively evaluated 50 HCM patients and 50 patients without significant cardiovascular disease (controls) who underwent clinically-indicated CMR. We performed a multivariate regression analysis adjusting the model for age, coronary artery disease, NYHA class, late gadolinium enhancement and LV EF with endpoints of ventricular tachyarrhythmias (VTA) and heart failure hospitalization (HFH). LA indexed volumes (LAVi), LA EF, expansion index, reservoir (εR), conduit (εCD), and contractile strain (εCT) were measured.

Results:
The mean age for HCM patients was 59.6 ± 16.3 (54% males) versus 50.9 ± 14.6 (36% male) for controls. Median follow up was 15.6 months. HCM patients had significantly higher LV mass, LV wall thickness, LAVi and lower LA strain compared to controls. On multivariate analysis, LA εCT, minimum and maximum LAVi were significantly associated with the composite outcome (p = 0.05). Cox proportional hazard models (figure) showed a clear difference in the outcomes around median εCT and maximum LAVi.

Conclusion:
HCM patients had significantly higher LAVi and lower LA strain compared to controls. LA εCT, minimum and maximum LAVi were significantly associated with the composite outcome of VTA or HFH.
Abstract 12159: Trends in Subsequent Myocardial Infarction Hospitalizations and Inpatient Mortality Among Cancer Patients With Prior Myocardial Infarction
Authors: Jain Akhil , Singh Sandeep , Akbariromani Hanieh , Mozaffari Mohammad Ali , Gudiwada Mohan Chandra Vinay Bharadwaj , Gaddam Vinuthna , AHMADZADEH Nazanin , Perera Ayodya , Naseem Hamna , Lankala Chetan Reddy , Chhayani Hiren , Desai Rupak
Published: June 2023

Background:
Patients hospitalized with subsequent/recurrent myocardial infarction (MI) suffer from high morbidity and mortality burden. Owing to the lack of contemporary data on cancer patients, we aimed to study the trends of subsequent Mi in this population. recurrent MI admissions and mortality in patients with prior history of MI and active cancer diagnoses.

Methods:
The National Inpatient Sample (2016-2019) was queried to identify adults with an active cancer diagnosis and prior MI hospitalization for subsequent MI admissions. Primary outcomes were nationwide trends in subsequent MI admissions and in-hospital mortality with sex and racial disparities. Trend analysis was performed by linear-by-linear regression method.

Results:
Cancer patients with prior MI (n=470755, median age 75 [IQ 67-82 years]) had 5.6% (26320) subsequent MI admissions. Subsequent MI hospitalizations mostly had male (69.3%), white (81.5%), enrolled in Medicare (81.1%), and South (31.1%) region admissions. Subsequent MI patients had higher complicated hypertension (58.4 vs 39.3%), diabetes with chronic complications (33 vs 21.4%), drug abuse (2.3 vs 1.4%) and obesity (13.6 vs 10.6%) than patients without subsequent MI. Subsequent MI admissions had a declining trend from 2016 to 2019 for both sex and all races except Hispanics (p
trend
<0.05)
[Fig. 1a].
All-cause in-hospital mortality showed a significant declining trend for males (p
trend
<0.05), but a marginal increase was seen in females
[Fig. 1b].
Furthermore, stratified by race, no significant change in mortality trend was noticed.

Conclusion:
There were declining trends in subsequent MI hospitalizations in cancer patients with prior MI in all sex/racial groups except in Hispanics. Males had improved outcomes in terms of in-hospital mortality, however, this improvement was not evident in females and on racial stratification.