bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15577: Diagnostic Performance of Cadmium-Zinc-Telluride Single-Photon Emission Computed Tomography versus Coronary Angiography Fractional Flow Reserve in Estimating Myocardial Blood Flow and Flow Reserve: A Diagnostic Accuracy Meta-Analysis
Authors: Elfaituri Muhammed K , BenGhatnsh Ahmed , Faraj Hazem Abdelkarem A , Khaled Taha , Msherghi Ahmed
Published: December 2023

Introduction:
Precisely estimating myocardial blood flow and flow reserve is crucial in diagnosing and managing ischemic heart disease. Coronary angiography fractional flow reserve (FFR) has been a standard tool. However, the recent emergence of Cadmium-Zinc-Telluride Single-Photon Emission Computed Tomography (CZT-SPECT) has provided an innovative diagnostic approach. Consequently, a comprehensive comparative analysis of their efficacies in evaluating myocardial blood flow and flow reserve is necessary.

Hypothesis:
This study aims to determine the diagnostic accuracy of CZT-SPECT compared to coronary angiography FFR in estimating myocardial blood flow and flow reserve.

Methods:
A systematic search until July 2022 was conducted across databases such as PubMed, Embase, and Web of Science, focusing on studies comparing CZT-SPECT and coronary angiography FFR in the estimation of myocardial blood flow and flow reserve. Utilizing the mada package in R software (version 4.0.3), we conducted diagnostic accuracy analysis by pooling metrics like sensitivity, specificity, false-positive rate estimates, diagnostic odds ratio, and positive and negative Likelihood Ratios (LR), all of which were presented with a 95% Confidence Interval (CI).

Results:
The meta-analysis incorporated 6 studies with a total patient population of 346. Our findings reveal that CZT-SPECT exhibited a pooled sensitivity of 79.1% (95% CI: 71.8-84.9%, I^2=0) and a specificity of 78.5% (95% CI: 70.4-84.8%, I^2=25.3%). The false-positive rate was 21.5% (95% CI: 15.2-29.6%). Moreover, CZT-SPECT demonstrated a diagnostic odds ratio of 13.75 (95% CI: 7.67-24.65), while the positive likelihood ratio was 3.67 (95% CI: 2.59-5.19), and the negative likelihood ratio stood at 0.26 (95% CI: 0.19-0.37).

Conclusions:
This study provides valuable insights into the diagnostic accuracy of CZT-SPECT compared to coronary angiography FFR in estimating myocardial blood flow and flow reserve. These findings indicate that while CZT-SPECT shows promising diagnostic potential, its performance is similar to coronary angiography FFR. The results will be instrumental in informing clinical decision-making and shaping future research directions in the field of cardiovascular imaging.
Abstract 15579: Stem Cell Modeling of a Candidate Genetic Variant in a Family With Complex Inherited Cardiomyopathy
Authors: Kirillova Anna , Jiang Siyi , Al Aaraj Yassmin , Reuter Chloe , Yue Yunshan , Rao Rashmi , Creager Michael , Barndt Robert , Wu Haodi , Scott Stuart , Okawa Satoshi , Parikh Victoria N , Chan Stephen Y
Published: December 2023

Introduction:
Inherited cardiomyopathies, such as arrhythmogenic right (or left) ventricular cardiomyopathy (ARVC; ALVC) and dilated cardiomyopathy (DCM), can lead to sudden cardiac death. Mechanisms of arrhythmogenesis in these cardiomyopathies are not fully understood, with ~ 20% of patients carrying a pathogenic variant in a validated cardiomyopathy-associated gene.

Aims:
Here, we investigate a family with highly variable expression of arrhythmogenic cardiomyopathy. The two affected siblings have differential ventricle involved and arrhythmia burden: with one fulfilling criteria for ARVC, and the other for ALVC. Their father has a non-ischemic cardiomyopathy with ventricular arrhythmias and a family history of sudden death. The maternal side is unaffected. The sibling with ALVC harbors a paternally inherited rare missense variant of uncertain significance (VUS) in plakoglobin (
JUP)
(c.356C>T; p.Pro119Leu), an ARVC-associated gene that does not segregate in the sibling with ARVC.

Hypothesis:
Study of patient-specific inducible pluripotent stem cell-derived cardiomyocytes (iPSC-CM) can define an elusive genetic etiology as well molecular pathways associated with cardiomyopathy in the affected family members.

Methods:
We reprogrammed iPSC lines from 3 affected family members and 2 unaffected maternal controls and differentiated them into cardiomyocytes.

Results:
Differentiation to iPSC-CMs resulted in transcriptionally upregulated markers of cardiac stress and contractile function in affected family members (
NPPA, NPPB, MYH7
). iPSC-CM harboring
JUP
c.356C>T did not differ in plakoglobin RNA or protein expression. Hypertrophy was observed in the iPSC-CMs from affected family members after isoproterenol stimulation. Whole exome sequencing results revealed rare candidate variants (MAF<5x10
-5
, REVEL>0.7) that segregated in affected family members.

Conclusions:
iPSC-CMs from affected family members recapitulate cardiomyopathy phenotypes. Affected family members harbor novel candidate variants not previously associated with cardiomyopathies. Future work will utilize base editing to evaluate for compound contributions of several novel VUS on cardiomyopathy phenotypes in iPSC-CM from family members.
Abstract 15580: Blood Transfusion in Ascending Aortic Surgery: No Inherent Cause for Concern
Authors: Kalyanasundaram Asanish , Velasquez Camilo , Zafar Mohammad , Ziganshin Bulat A , Elefteriades John A
Published: December 2023

Introduction:
There is widespread concern that blood transfusion has a strong adverse impact on early/late surgical survival, so hematocrit is often allowed to drift very low. We investigate whether this adverse impact of transfusion is seen in aortic surgery.

Methods:
The records of 870 patients who underwent open ascending aortic or arch surgery from 2004 to 2016 by one surgeon at a large hospital were reviewed. Of these patients, 347 (39.9%) received a blood transfusion. The mean number of intra-op units transfused was 0.89, and the mean total units transfused (intra+post-op) was 2.45. High-volume transfusion (over 5 units) was needed for only 24 (6.9%) patients. We aimed to maintain a post-operative Hct of above 28%. Mean follow-up was 6.5 years.

Results:
We found no significant difference in 30-day or 1-year mortality between the transfused and non-transfused groups, nor between high- and low-volume transfused patients. However, the long-term mortality beyond 1 year was higher in the transfused group than in the non-transfused group (13% vs 5.7%; p=0.0003). Notably, the transfused group was older than the non-transfused group (64.9 vs 57.7). On Kaplan-Meier analysis (Fig.1), there remained a significant adverse effect of transfusion overall (p=0.004), but this effect was eliminated if patients were propensity matched for age (p=0.18). There was no difference in high- vs low-volume K-M survival (p=0.58). Amongst those transfused, the total units transfused was not a predictor of mortality in any time-frame on multivariate regression when adjusting for pre-op Hct, blood transfusions, DHCA, type A dissection, and operation urgency (p=0.95, 0.56, and 0.45 for 30d, 1yr, and beyond 1yr respectively).

Conclusions:
Transfusion and transfusion volume had no significant effect on early mortality, or even on late mortality after appropriate age adjustment. Should patient condition warrant, surgeons need not be concerned that transfusion will further reduce survival.
Abstract 15582: Robotic-Assisted versus Conventional Mitral Valve Repair: An Updated Meta-Analysis of Operative and Post-Operative Outcomes
Authors: Elfaituri Muhammed K , Khaled Ala , BenGhatnsh Ahmed , Khaled Taha , Faraj Hazem Abdelkarem A , Msherghi Ahmed
Published: December 2023

Introduction:
Cardiac surgery has seen notable advancements, especially in mitral valve repair, with the emergence of robotic-assisted mitral valve repair (RAMVR). Amid ongoing debates about RAMVR's efficacy and safety versus conventional mitral valve repair (CMVR), this updated meta-analysis offers a comprehensive comparison based on recently published data.

Aim:
The study aims to provide a comparison of RAMVR and CMVR, focusing on key operative and postoperative outcomes.

Methods:
A systematic search was conducted utilizing databases such as PubMed, EMBASE, and the Cochrane Library, until January 2023. The inclusion criteria included studies that compared RAMVR with CMVR. The meta-analysis incorporated a random-effects model to calculate pooled mean differences (MD) and relative risks (RR). All statistical analyses were carried out using R software (version 4.0.3), by metafor and meta packages.

Results:
Ten studies with a total of 54,235 patients (5,092 in the RAMVR group and 49,143 in the CMVR group) were included. The meta-analysis showed that RAMVR was associated with a significantly shorter hospital stay (MD -1.79 days; 95% CI -2.77 to -0.83, P=<0.01, I2=100%) and ICU length of stay (MD -16.76 days; 95% CI -29.34 to -4.19, P=<0.01, I2=98%). However, RAMVR was associated with significantly longer cardiopulmonary bypass time (MD 42.90 minutes; 95% CI 29.58 to 56.22, P<0.01, I2=98%) and cross-clamp time (MD 29.67 minutes; 95% CI 19.84 to 39.51, P<0.01, I2=98%). In terms of relative risks, RAMVR had a lower rate of overall mortality (RR 0.55; 95% CI 0.42 to 0.74, P<0.01, I2=0%) and rate of infection (RR 0.62; 95% CI 0.52 to 0.74, P<0.01, I2=0%). However, there was no statistically significant difference in the rate of blood transfusion, stroke rate, atrial fibrillation, and transient ischemic attack.

Conclusions:
This study suggests that RAMVR may offer benefits such as shorter hospital and ICU stays and lower overall mortality and infection rates, but it also involves longer cardiopulmonary bypass and cross-clamp times. Given the high heterogeneity across the included studies, this underlines the importance of further high-quality randomized controlled trials to optimize RAMVR techniques for improving patient outcomes in mitral valve repair.
Abstract 15584: Artificial Intelligence-Guided Screening for Atrial Fibrillation Detection Among Patients With Different Socioeconomic Status
Authors: Kalinoski-DuBose Victoria , Yao Xiaoxi , Noseworthy Peter A , Deng Yihong , Attia Zachi , Lopez-Jimenez Francisco , Gersh Bernard J , Graff-Radford Jonathan
Published: December 2023

Introduction:
Recently, an artificial intelligence (AI) algorithm was validated for identifying ECG signatures of atrial fibrillation (AF) risk during normal sinus rhythm. Traditionally, socioeconomically disadvantaged populations are less likely to receive novel or guideline-recommended treatments, and have high chronic disease burden, including cardiovascular diseases. There have also been concerns about new technologies creating a digital divide, worsening existing health disparities.

Hypothesis:
An AI algorithm will detect AF risk unequally across patients with different levels of social determinants of health (SDOH).

Methods:
The initial prospective, non-randomized, interventional study leveraged EHR and digital technologies to prospectively enroll 1004 patients with a broad range of AI-ECG risks of AF, who received continuous cardiac rhythm monitoring for up to 30 days. The Area Deprivation Index (ADI) was used as a composite measure of SDOH which is comprised of indicators spanning four domains: income, education, employment, and house quality. 904 intervention patients linked to the ADI data were matched to 904 real-world control patients derived from eligible but unenrolled patients. Those with ADI under 33% were defined as having better SODH; and patients with ADI above 33% were defined as having worse SODH.

Results:
Median age was 74 years and 38% were women. After matching, the intervention and control arms were balanced in all baseline characteristics, including HF, HTN, diabetes, stroke, CAD and ADI. A hazard ratio of 3.11 (P<0.001) was computed when comparing intervention to control for primary AF diagnosis outcome. In patients with worse SDOH, the intervention increased AF detection from 2.6% to 8.8% (HR 3.63 [2.09, 6.32]); in the better SDOH, the intervention increased AF detection from 3.9% to 9.3% (2.41 [1.23, 4.74]).

Conclusions:
An AI-guided AF screening program increased the detection of AF in both patients with better or worse SDOH. The current study validates the use of AI in historically disadvantaged populations displaying the possibility for broad implementation with decreased possibility of perpetuating disparities.
Abstract 15645: Budget Impact Analysis of PrecisionCHD, an Artificial Intelligence Guided, Integrated Genetic-Epigenetic Test for Assessing CHD, Demonstrates Extensive Cost Savings Compared to Conventional Methods
Authors: Dogan Meeshanthini , Frisvold David , Abdullahi Khullani , Dogan Tim , Philibert Robert
Published: December 2023

Coronary heart disease (CHD) costs the United States healthcare system at least $216 Billion in treatment cost and $147 billion in lost productivity annually. Therefore, there is an urgent need for cost-effective solutions to reduce both the human and economic burden of CHD. Because the initial CHD diagnostic approach has a large impact on subsequent costs and healthcare outcomes, risk bearing entities are keen to determine the optimal algorithmic approach for guiding the use of CHD diagnostic tools. In order to better understand the economic and clinical impact of a newly developed Precision Epigenetic test for assessing CHD status, PrecisionCHD, we conducted a budget impact analysis comparing the use of PrecisionCHD to the use of conventional exercise ECG and coronary computed tomographic angiography (CCTA) (in a 75:25 ratio) as the initial diagnostic assessment of CHD using nationally published cost estimates, generally accepted side effects, sensitivity and specificity metrics for each test, with all positive tests resulting in the initiation of moderate to high dose statin therapy as per treatment guidelines. Our analysis showed that for an insurance plan with 1 million covered individuals, a $20 co-pay for office visits and 10% co-insurance, the use of PrecisionCHD over exercise ECG and CCTA would result in $92 million in annual cost savings with a significant portion of those savings being secondary to the inferior performance of exercise ECG. Increasing the number of CCTA test performed increases the number of CHD cases detected, but also results in greater costs including costs secondary to contrast dye induced kidney damage. We conclude that the use of PrecisionCHD for CHD detection can improve healthcare outcomes and decrease CHD related costs. Given current trends in the developments in epigenetics-based approaches, it is likely that this advantage will increase further.
Abstract 15653: Heart Failure Medications Have a Direct Inhibitory Effect on Endothelial-to-Mesenchymal Transition in an
in vitro
Model
Authors: Krishnamoorthi Muthu Kumar , Thandavarayan Rajarajan A , Bhimaraj Arvind
Published: December 2023

Introduction:
Endothelial-to-Mesenchymal Transition (EndoMT) is a process where endothelial cells can transform into mesenchymal cells. This mechanism, while well established in embryogenesis and cancer, has been accumulating evidence as a contributor to cardiovascular diseases including heart failure (HF). While current guideline-directed medications (GDMT) for HF have postulated benefits to help cardiomyocytes and the heart, further investigation on the specific impact of HF drugs on this pro-fibrotic mechanism of EndoMT is required.

Hypothesis:
We hypothesize that HF drugs can inhibit EndoMT in an
in vitro
model

Methods:
Human umbilical vascular endothelial cells (HUVECs) were incubated for 24 h with the drugs - metoprolol, losartan, lisinopril, dapagliflozin, and valsartan/sacubitril, at concentrations ranging from 1 mg to 1 ng per mL, to evaluate cell viability using alamarBlue
TM
assay.
In vitro
EndoMT is induced with Nω-Nitro-L-arginine methyl ester hydrochloride and angiotensin II in HUVECs. During EndoMT, HUVECs were co-incubated with the drugs to determine their effect on EndoMT. Immunofluorescence for Endothelial (VE-Cadherin) and Mesenchymal (Transgelin) markers was used to characterize EndoMT.

Results:
All the HF drugs tested had a dose-dependent effect on HUVEC viability. The highest drug concentration (1 mg/mL) resulted in cell death while lower concentrations (1 μg to 1 ng per mL) did not affect cell viability. A concentration of 1 μg/mL was used to investigate the drugs’ effect on EndoMT. Immunofluorescence staining revealed reduced levels of expression for Transgelin in HUVCEs induced to undergo EndoMT in the presence of the treated drugs compared to the untreated and vehicle-treated cells after 4 days of incubation.
Conclusion
All the HF medications inhibited EndoMT in an in vitro model. Our results show that some of the beneficial effects of the HF GDMT medications used in clinical practice could be through an inhibitory effect on EndoMT.
Abstract 15669: Proteomic Associations With Late-Life Cardiac Structure and Function: The Atherosclerosis Risk in Communities Study
Authors: Yang Yimin , Lamberson Victoria , Claggett Brian , Tin Adrienne , Hoogeveen Ron C , Matsushita Kuni , Ballantyne Christie M , Coresh Josef , Yu Bing , Shah Amil M
Published: December 2023

Introduction:
Alterations in cardiac structure and function underlie heart failure (HF). Identification of novel markers of cardiac function may provide insights into HF pathophysiology.

Methods:
Among 4253 participants in ARIC who were free of HF and atrial fibrillation at study Visit 5 (2011-13) and had aptamer-based proteomics (SomaScan v4), we used exploratory factor analysis to reduce 21 echocardiographic measures (2D, spectral and tissue Doppler, strain) to 5 factors. We assessed the association of 4955 plasma proteins with each factor using multivariable linear regression. Hierarchical clustering grouped proteins associated with ≥1 factor by their pattern of association with the factors. Association of protein levels with incident HF post-Visit 5 was assessed using multivariable Cox models. Two-sample Mendelian randomization (MR) was performed to evaluate potential causal effects of proteins on HF and left/right ventricular (LV/RV) size & function.

Results:
Mean age was 75±5 years, 41% were male, 17% reported Black race. We identified 5 factors representing: cardiac structure, LV myocardial motion, LV chamber level contractility, LV filling pressure, and RV myocardial motion. 409 proteins were significantly associated with ≥1 factor, 101 of which were significantly associated with HF. Hierarchical clustering grouped proteins into 6 clusters (Figure). The 54 proteins in Cluster 5 demonstrated consistent associations across all factors and were enriched for proteins associated with HF. MR identified 7 proteins, including CHST15 - a sulfotransferase involved in proinflammatory cytokine biosynthesis - which demonstrated potential causal effects on HF and on LV/RV volume.

Conclusion:
We uncovered a subset of plasma proteins associated with multiple dimensions of cardiac structure and function and with HF risk. A subset, including CHST15, had potential causal effects on cardiac structure/function and HF and warrant further investigation.
Abstract 15688: Association of Cytochrome P450 2C19 Polymorphism With Ischemic and Bleeding Risk in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention
Authors: Gjermeni Diona , Szabo Sofia , Anfang Viktoria , Vetter Hannah , Hesselbarth David , Leggewie Stefan , Trenk Dietmar , Duerschmied Daniel , Westermann Dirk , Olivier Christoph B
Published: December 2023

Introduction:
CYP2C19 isoenzymes of cytochrome P450 impact the effect of clopidogrel. Guidelines recommend clopidogrel in addition to oral anticoagulation (OAC) in patients with atrial fibrillation (AF) after percutaneous coronary intervention (PCI). This study aimed to evaluate the association of CYP2C19 polymorphism with ischemic and bleeding risk in patients with AF undergoing PCI.

Methods:
Patients with AF and an indication for OAC were included in this two-center prospective cohort study up to 3 days after PCI. Carriers of ≥1 loss of function (LOF) allele CYP2C19*2 were classified as poor metabolisers (PM). Carriers of ≥1 gain of function allele (GOF) were defined as rapid metabolisers (RM). Normal metabolisers (NM) were defined as absence of LOF and GOF alleles. Primary outcome was defined as death, myocardial infarction, or stroke (MACE) at 6 months ±2 weeks. Secondary outcome was defined as non-major clinically relevant (NMCR) or major bleedings.

Results:
283 patients were included in the study. Median age was 78 (interquartile range, IQR 72-82) years old and 204 (72%) were males. All patients received treatment with clopidogrel and OAC. 73 (26%) were PM, 108 (38%) were NM and 102 (36%) RM. The primary ischemic outcome occurred in 22 (8%) and the secondary outcome in 38 (13%) patients. PM status did not significantly associate with primary ischemic outcome (PM: 6 [8.2%] vs. NM+RM: 16 [7.6%]; odds ratio, OR 1.09 [95% confidence interval 0.41-2.89], p=0.805). RM status did not significantly associate with bleeding (RM: 14 [13.7%] vs. PM+NM: 24 [13.3%]; OR 1.04 [0.51-2.12], p=1.00). Bleeding rates tended to be lower for patients with PM status (major, NMCR, or minor bleeding: PM 12 [28.7%] vs. NM+RM 84 [40.0%]; 0.61 [0.34-1.07], p=0.09).

Conclusions:
This pilot study of patients with oral anticoagulation for atrial fibrillation and clopidogrel after PCI ruled out, with 95% confidence, a ≥3-fold increase of ischemic risk for carriers of ≥1 loss of function allele CYP2C19*2 compared with non-carriers. This study was underpowered to detect less pronounced associations. LOF-carrier status might protect from bleeding.
Abstract 15718: Valvulo-Arterial Impedance in ESKD Patients With Aortic Stenosis: Echocardiographic Correlates and Outcomes
Authors: Ogugua Fredrick , Zellmer Lucas , Mathew Roy O , Shroff Gautam R
Published: December 2023

Introduction:
Higher values of valvulo-arterial impedance (Zva), a marker of global hemodynamic load, are associated with worse outcomes in patients with aortic stenosis (AS). No studies have evaluated the impact of Zva on outcomes in end stage kidney disease (ESKD) patients with AS.

Objectives
We aim to evaluate clinical outcomes associated with Zva and echocardiographic correlates of Zva in patients with AS and ESKD.

Methods:
Consecutive ESKD patients on dialysis with AS on echocardiography from a single center between January 2000 and March 2021. AS severity was defined using AHA guideline recommendations. Zva [units: mmHg/ml/m
2
] was calculated as (systolic arterial pressure + aortic valve mean gradient) divided by indexed stroke volume. The association of high Zva with the combined primary outcome of aortic valve replacement (AVR) or mortality was assessed using Cox proportional hazard analysis.

Results:
The cohort included 94 patients with co-prevalent ESKD and AS; mean age 66 years, 71% male; 43% Black, 24% severe AS. Patients with Zva>4 mmHg/ml/m2 (median value;
Table
) associated with lower indexed aortic valve area (0.52 vs. 0.71 cm
2
/m
2
, p<0.001), lower stroke volume (66 vs. 84 ml; p<0.001), lower cardiac output (5.3 vs. 6.1 L/min; p=0.005);
Figure
. Zva did not associate with the combined incidence of AVR or mortality (p=0.2).

Conclusion:
In ESKD patients with AS, high Zva was associated with smaller AVA and measures of low flow state; but not with the primary outcome of AVR or mortality. These findings should be validated in a larger cohort. Differences in prognostic information from Zva and flow states in the context of AS between ESKD vs non-ESKD patients deserve further study.
Abstract 15721: CRISPR Activates Heterochromatic Cardiac Genes in Fibroblasts to Initiate Lineage Conversion Into Cardiac Progenitors
Authors: DUTTA SUCHANDRIMA , LIANG JIALIANG , Huang Wei , He Xingyu , Paul Christian , Wang Yi-gang
Published: December 2023

Introduction:
Our previous studies have demonstrated that CRISPR activation (CRISPRa) of endogenous genes was sufficient to convert fibroblasts into induced cardiovascular progenitor cells (iCPCs) for myocardial regenerative therapy. However, reprogramming efficiency remains a challenge and little has been elucidated about the epigenetic mechanisms of cellular reprogramming, which will be important for methodological improvements or refinements.

Hypothesis:
CRISPRa complex can alter the chromatin accessibility and activity of heterochromatic cardiac genes in fibroblasts, directly initiating cardiac reprogramming.

Methods:
A fibroblast-specific CRISPRa mice model (Pdgfra-cre/ERT; ROSA-dCas9-SunTag) was generated. SgRNAs targeting the promoter region of
Gata4, Isl1, Nkx2-5, Baf60c,
or
Tbx5
genes were transduced through an AAV system in cardiac fibroblast isolated from transgenic mice. iCPCs were confirmed via immunostaining of CPC markers and cardiac electrophysiological assays. iCPCs were collected for RNA-seq, ATAC-seq, and ChIP-seq after reprogramming induction to reveal the epigenetic landscape modulated by CRISPRa.

Results:
The CRISPRa system was activated in ~80% of fibroblasts after tamoxifen induction and AAV-sgRNA transfection. The reprogrammed iCPCs were characterized by immunostaining of proliferative markers (Ki67 and Pcna), progenitor surface markers (Flk1 and Ssea1), and markers of cardiac tri-lineage cells after induced differentiation. RNA-seq data showed the upregulation of genes associated with cell cycling (Cdkn1b, Aurkb, etc.) and heart development (Myh6, Irx4, etc.) in CRISPRa-induced cells. ATAC-seq showed increased chromatin accessibility at the loci of cardiogenic genes targeted by CRISPRa in fibroblasts. Furthermore, ChIP-seq of Gata4, Nkx2.5, and Tbx5 associated DNA shows that these factors can bind to their own promoter regions in fibroblasts after CRISPRa induction.

Conclusions:
CRISPRa complexes open the chromatin of the targeted genes in fibroblasts and establish an endogenous autoregulatory loop to ensure stable reprogramming into cardiac progenitors.
Abstract 15724: All-Cause Death and Major Adverse Events in Atrial Fibrillation With Frailty: Observations From the Korea National Health Insurance Service Data
Authors: Park Jong Sung , Yang Pil-sung , Kim Daehoon , Sung Jung-Hoon , Jang Eunsun , Yu Hee Tae , Kim Tae-Hoon , Pak Hui-Nam , LEE Moon Hyoung , JOUNG BOYOUNG
Published: December 2023

Introduction:
Atrial fibrillation (AF) may be a marker of frailty. Previous evidence indicated that frailty in patients with AF has been associated with increased adverse events.

Hypothesis:
This study aimed to investigate the effect of frailty on the use of oral anticoagulants (OAC) and clinical outcomes in a nationwide cohort of patients with AF.

Methods:
We included 451,368 participants without AF from the Korea National Health Insurance Service-Health Screening cohort from 2005 to 2010. Patients’ Hospital Frailty Risk Score was calculated and patients were divided into two groups: without frailty (< 5 points) and with frailty (≥ 5 points).

Results:
Over 7.2 years, 11,953 participants (median age, 67 years; 60.2% men) developed new-onset AF. Among these patients, 26.9% had frailty. Frailty was significantly associated with older age, female sex, polypharmacy, and comorbidities. Frailty was negatively associated with OAC prescription after new-onset AF (
P
< 0.001). Patients with frailty had significantly higher risk of all-cause death (hazard ratio [HR] 2.87, 95% confidence interval [CI] 2.66-3.11), cardiovascular death (HR 2.60, 95% CI 2.77-2.98), stroke (HR 2.49, 95% CI 2.25-2.75), major bleeding (HR 2.54, 95% CI 2.28-2.83), and heart failure admission (HR 1.30, 95% CI 1.11-1.53). The increased risks of all-cause death, cardiovascular death, stroke, and heart failure admission due to frailty were lower with OAC prescription.

Conclusions:
Frailty was negatively associated with OAC use and was a predictor of worse prognosis. However, the increased risks associated with frailty were reduced by OAC in patients with AF.
Abstract 15735: Antibody-Based Plasma Proteomics Profiling Reveals New Markers of Cardiorespiratory Fitness
Authors: Fredrickson Katie , Manish Mahesh , Barber Jacob , Deng Shuliang , Rao Prashant , Mi Michael , Dev Prasun K , Farrell Laurie , Clish Clary , Bouchard Claude , Gerszten Robert E , Sarzynski Mark A , Robbins Jeremy M
Published: December 2023

Background:
Plasma proteins can be biomarkers of cardiovascular health status but also physiologic effectors that mediate health benefits. Cardiorespiratory fitness (CRF) is an integrative measure of cardiovascular and metabolic health and independent predictor of future cardiovascular disease (CVD) and mortality risk, however limited knowledge exists regarding its molecular transducers. We sought to expand upon prior proteomic studies of CRF using an antibody-based technology (Olink
TM
).

Hypothesis:
Olink proteomic profiling will identify new markers and potential mediators of CRF.

Methods:
We measured plasma proteins (N=1,472) using Olink’s platform in a pilot study within the HERITAGE Family Study (N=209 participants, mean age=34 years, 56% female, 36% Black) before and after 20 weeks of endurance exercise training (ET). We performed multivariable linear regression to measure the association between protein levels and CRF measured by CPET (VO
2
max in ml*kg
-1
*min
-1
) adjusting for age and sex. Lean body mass was measured by hydrostatic weighing. Protein changes after ET were assessed using paired Student’s t-tests.

Results:
We identified 70 proteins significantly associated (FDR q <0.05) with VO
2
max. Among these, 14 have not previously been measured in the context of CRF, including perilipin-1, a modulator of lipid homeostasis in adipocytes (beta=-3.8, q=2.4x10
-4
); latent-transforming growth factor beta-binding protein 3 (beta=-2.6, q=1.3x10
-3
), a key regulator of TGF-beta activation; and hydroxysteroid 11-beta dehydrogenase 1 (beta=3.2, q=1.2x10
-3
), which regulates cortisol metabolism. Carbonic anhydrase (CA) XIV (CA14; beta=5.4, q=1.3x10
-8
), a member of the CA family with extracellular activity, had the strongest positive association with VO
2
max in our primary model as well as after further adjusting VO
2
max for lean body mass. Further, CA14 levels increased significantly after ET (log2 fold change: 0.14, q=0.007).

Conclusions:
Antibody-based plasma proteomics profiling identified new markers of CRF, including a CA isoform that increases after ET. These findings motivate further study of CA14’s mechanistic role in CA14 and expanded proteomics profiling to investigate molecular transducers of CRF.
Abstract 15739: Fetal Echocardiographic Predictors of Perinatal Outcome in Congenital Atrioventricular Block
Authors: Conn Nina A , Lipsitz Stuart , Sleeper Lynn A , Tworetzky Wayne , Gellis Laura , Schidlow David N , Friedman Kevin G
Published: December 2023

Background:
Congenital atrioventricular block (AVB) is a rare disease with poor outcomes. Heart rate (HR) is a major prognostic factor. To date, no study has evaluated the contribution of cardiac output (CO), stroke volume (SV), and HR on outcomes.

Methods:
In this retrospective study we evaluated associations between fetal echocardiographic parameters and risk of a composite severe fetal adverse event (AE) in patients with congenital AVB.

Results:
Of the 58 cases of congenital AVB, 21 (36%) had the composite AE, defined as fetal hydrops (8/58, 14%), ≥ moderate ventricular dysfunction (LV 3/58, 5%; RV 6/58 11%), fetal demise (2/57, 4%), or premature birth at ≤ 35 weeks (17/55, 31%). Of the 55 live births, 3/55 (5%) patients died and 35/55 (64%) had a pacemaker placed in the neonatal period. In univariate analysis, lower HR z-score was associated with the composite AE (p = 0.002) and all individual components of the composite AE. Higher LV end diastolic volume was associated with the composite AE (p = 0.004), premature birth (p = 0.006) and neonatal pacemaker placement (p = 0.009). Higher LV SV was associated with the composite AE (p = 0.003) and with fetal hydrops (p = 0.031) and premature birth (p = 0.002). Higher combined CO (p = 0.038), presence of structural heart defect (p = 0.038) and heterotaxy (p = 0.01) were associated with fetal hydrops. In multivariate analysis, lower HR z-score (p = 0.044) and higher LV SV (p = 0.037) were associated with the composite AE. Longitudinal analysis showed the AE group had lower HR and higher SV throughout gestation and trends towards a greater decline in SV and CO (particularly RV CO) in the third trimester.

Conclusions:
Heart rate, not CCO, is the primary determinant of perinatal outcome in fetuses with high grade AVB. The compensatory increase in LV volume and SV in the patients with the lowest HR (and worst outcomes) maintains CCO in most fetuses with AVB and reflects the ability for fetal cardiac adaptation in the setting of prolonged severe bradycardia.
Abstract 15741: Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Individuals With Obesity or Overweight but Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Moiz Areesha , Levett Jeremy , Filion Kristian B , Peri Katya , Reynier Pauline , Eisenberg Mark J
Published: December 2023

BACKGROUND:
Randomized controlled trials (RCTs) have demonstrated that semaglutide, a GLP-1 receptor agonist, results in clinically important weight loss among individuals with type 2 diabetes. However, its effect on sustained weight loss among those without diabetes is unclear.

Objective:
To examine the long-term efficacy and safety of once-weekly semaglutide use for weight loss among individuals with obesity or overweight but without diabetes.

Methods:
We systematically searched MEDLINE, Embase, and the Cochrane Libraries to identify RCTs that randomized participants with obesity or overweight but without diabetes to a once-weekly 2.4 mg subcutaneous dose of semaglutide versus placebo. Inclusion was restricted to RCTs that reported change in body weight at a follow-up duration of ≥ 68 weeks. The primary outcome was relative change in body weight from baseline to 68 weeks. Random-effects models with inverse variance weighting estimated weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs).

Results:
Three RCTs (n=2,783, 6.0% overweight [BMI 27 to 29.9 kg/m
2
] and 94.0% obese [BMI ≥30 kg/m
2
]) were included. Compared to placebo, once-weekly semaglutide was associated with decreased relative (WMD: -12.0%; 95% CI -13.9%, -10.2%; Table 1) and absolute body weight (WMD: -12.2; 95% CI -13.8, -10.6 kg) at 68 weeks. A total of 86.5% of participants randomized to semaglutide achieved ≥5% weight loss compared to 34.8% with placebo (RR: 2.41; 95% CI 1.26, 4.64). The incidence of gastrointestinal adverse events was higher with semaglutide (RR: 1.45; 95% CI 1.14, 1.84); however, the majority of these events were transient, mild-to-moderate in severity, and did not require treatment discontinuation. A low incidence of serious adverse events was reported (9.5%).
CONCLUSIONS:
Among individuals with obesity or overweight but without diabetes, semaglutide is efficacious for sustained weight loss.
Abstract 15772: From Agony to Relief: Overcoming Angina Through Endovascular Coiling of the Left Internal Mammary Artery (LIMA) to Pulmonary Artery (PA) Fistulae- A Case Report
Authors: Kieserman Jake M , Colello Stephanie , Fiorilli Paul
Published: December 2023

Introduction:
LIMA to PA fistulae are a rare complication after coronary artery bypass graft (CABG) surgery. We present a patient with angina secondary to a steal syndrome from LIMA-PA fistulae, treated with endovascular coiling.

Case:
The patient is a 49-year-old active male with coronary artery disease, status post CABG at age 46 with a LIMA graft to the left anterior descending artery, radial artery graft to the first obtuse marginal artery, and saphenous venous graft (SVG) to the posterior descending artery. At age 48, he developed angina and underwent stent placement to the distal right coronary artery after the SVG was found to be occluded. Several months later, he reported dyspnea and chest pain on exertion. An exercise nuclear stress test showed abnormal myocardial perfusion in the anteroseptal region, and he was referred for left heart catheterization (LHC). LHC revealed unchanged native coronary disease, patent LIMA, and a network of collateral vessels from the LIMA feeding into the pulmonary vasculature (Figure 1). The collaterals were not seen on LHC 9 months prior. CT coronary angiography confirmed multiple fistulae originating from the superior aspect of the LIMA graft communicating with the PA (Figure 1). After a multidisciplinary, patient-centered, heart team discussion, he underwent successful endovascular coiling of the collateral branches (Figure 2).

Discussion:
LIMA-PA fistulae is a rare cause of angina and there is a paucity of literature on management. To our knowledge, coil embolization has been described in roughly 10 cases. Here, we present a successful case of endovascular coiling of collateral vessels leading to symptomatic improvement.
Abstract 15779: A Comparison of Survival Outcomes in Ischemic Cardiomyopathy Following Heart Transplantation Under 2018 Allocation Criteria
Authors: Chaudhry Talha , Aryan Zahra , Gardin Julius , Bello Juan
Published: December 2023

Introduction/Background:
The adult heart transplant allocation system was changed from a 3-tiered to a 6-tiered system in 2018, prioritizing unstable patients on temporary mechanical circulatory support and patients with non-ischemic cardiomyopathies on the waitlist.

Research Questions/Hypothesis:
This study aims to compare post-heart transplantation survival rates and all-cause mortality of ischemic and non-ischemic cardiomyopathies in the United States before and after the implementation of the current 6-tiered heart allocation system.

Methods/Approach:
The United Network for Organ Sharing registry was queried from 2011 to 2021 for all adults listed for isolated heart transplantation for the first time. The Kaplan-Meier method and Cox proportional hazards regression modeling were used to compare the post-transplantation outcomes between ischemic and non-ischemic cardiomyopathies.

Results:
A total of 21,104 cases were included in the final analysis. The 1, 5, and 10-year survival rates of ischemic versus non-ischemic cardiomyopathies were 89.7% vs. 92.1%, 76.5% vs. 81.5%, and 48.5% vs. 62.4%, respectively (p<0.001). The risk of all-cause mortality was greater in patients with ischemic cardiomyopathy (Hazard Ratio: 1.368, 95% CI, 1.285 - 1.457, p<0.001). Post heart transplant survival rate has decreased by approximately 2% since 2018 compared to the era of the prior allocation system (p<0.001).

Conclusions:
The gap between the survival rate of ischemic and nonischemic cardiomyopathies has not improved since 2011. The one-year survival rate has dropped by ~2% since 2018, partly due to the new heart allocation system prioritizing clinically unstable patients.
Abstract 15781: Associations Between Hysterectomy and Incident Metabolic Syndrome: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Broni Eric K , Echouffo Tcheugui Justin B , Palatnik Anna , Graham Ernest , Turkson-Ocran Ruth-Alma , Commodore-Mensah Yvonne , Ndumele Chiadi E , Michos Erin D
Published: December 2023

Background:
Metabolic syndrome is linked to increased risk of incident atherosclerotic cardiovascular disease (CVD), heart failure, and all-cause mortality. Notable associations exist between hysterectomy with bilateral salpingo-oophorectomy and metabolic syndrome. However, there is emerging evidence that even with ovarian conservation, hysterectomy independently increases long-term risk for CVD. Despite these associations, extant literature on the independent link between ovary-sparing hysterectomy and metabolic syndrome is scarce. We, therefore, examined the associations between hysterectomy with ovarian preservation and metabolic syndrome risk in a multi-ethnic cohort.

Methods:
We studied 1,355 female MESA participants who had data on self-reported history of hysterectomy, oophorectomy, and hystero-oophorectomy and were free of metabolic syndrome and CVD at exam 1 (2000-2002). Metabolic syndrome was defined by the NCEP Adult Treatment Panel III criteria. We used multivariable Cox regression models to evaluate the associations between hysterectomy/oophorectomy subgroups and incident metabolic syndrome from exams 2 (2002-2004) to 6 (2016-2018).

Results:
The mean ± SD age was 59.0 ± 9.5 years, with 42% White, 27% Black, 19% Hispanic, and 13% Chinese-American participants. 29% and 22% had a history of hysterectomy and oophorectomy, respectively. Over a median follow-up of 10.5 (3.01-17.62) years, there were 750 metabolic syndrome events. Hysterectomy [HR 1.32; 95% CI (1.01-1.73)] and hystero-oophorectomy [1.40 (1.13-1.74)] were strongly associated with metabolic syndrome
(Table)
.

Conclusion:
Hysterectomy with ovarian preservation is independently associated with a higher risk of metabolic syndrome. If our findings are confirmed by other studies, screening and preventive strategies focused on females with ovary-sparing hysterectomy and the pathways driving these associations should be explored.
Abstract 15795: Outcomes After Cardiac Implantable Electronic Devices Among People With and Without HIV
Authors: Xiao Sophia Y , Thakkar Anjali , Ma Yifei , Durstenfeld Matthew S , Hsue Priscilla Y
Published: December 2023

Introduction:
The long-term outcomes of cardiovascular implantable electronic devices (CIED) in people with HIV (PWH) is unknown despite higher rates of sudden cardiac death and heart failure in HIV.

Objective
To compare outcomes between PWH and the general population who have CIEDs.

Methods:
Retrospective cohort study of patients receiving care at two academic hospitals in San Francisco who got CIEDs (pacemaker, implantable cardioverter defibrillator, cardiac resynchronization therapy ± defibrillator) from 2000-2018. Since CIEDs were rarer in PWH than in those without HIV, we also did a nested case-control study. Case and controls were matched by age, sex, and CIED type. Death data was obtained from the National Death Index.

Results:
We identified 3,268 patients who got CIEDs; 1% was PWH. In PWH at CIED implantation, mean HIV duration was 19 years, mean CD4 count was 449 cells/uL, 78% had undetectable viral loads, and all were on antiretroviral therapy. PWH were younger than the control (mean age 62 vs. 69 years, p < 0.01). Both groups had similar rates of hypertension, diabetes, CAD, smoking, and drug use, but more PWH had hepatitis C than the control (25% vs. 3.0%, p < 0.01). Both groups had a similar number of pacemakers (56% vs. 58%, p = 0.86) and defibrillators (44% vs. 39%, p = 0.56). Post-procedure, five (16%) PWH had lead failure or infection while nine (14%) controls had lead failure. One PWH with site infection reported IV drug use. Post CIED placement, median survival in years was 5.3 in PWH vs. 6.4 in controls. No strong association between HIV status and survival (HR 1.9 [95% CI 0.7 to 5.0]) was seen (
F
igure
).

Conclusions:
To our knowledge, this is the first study looking at survival post CIED between PWH and the general population. Our findings suggest that the number of PWH getting CIEDs remains low despite no definitive evidence of procedural complications; and that PWH have similar survival to those without HIV. More studies exploring barriers to CIED placement in PWH are needed.
Abstract 158: Exploring the Potential for Kidney Donation in Out-of-Hospital Cardiac Arrest Cases With No Chance of Survival
Authors: Chocron Richard , Laurenceau Thomas , BEGANTON Frankie , Dumas Florence , Jouven Xavier
Published: December 2023

Introduction:
The global kidney shortage can potentially be addressed through the implementation of the uncontrolled donation after circulatory death (uDCD) pathway. However, the current Termination-of-Resuscitation (TOR) rules, although effective in identifying futile resuscitation, do not consider the potential benefits of organ donation.

Objective:
This study aims to assess the potential pool of uDCD kidney donors among patients with resuscitation attempts by Emergency Medical Services (EMS) who meet TOR criteria.

Methods:
Retrospective analysis was conducted using data from the Paris Sudden Death Expertise Center (SDEC) registry spanning from 2011 to 2020. TOR criteria evaluation and identification of potential organ donors were performed using established selection criteria from previous protocols on TOR rules and uDCD. Incidence rates (per patient-years) were calculated using data from the National Institute of Statistics and Economic Studies.

Results:
Out of 19,976 cases of Out-of-Hospital-Cardiac Arrest (OHCA) with resuscitation attempts by EMS, 12,890 (64.5%) did not achieve sustained Return of Spontaneous Circulation (ROSC). Among patients with no successful ROSC, the annual number and incidence of patients with no chance of survival varied across different TOR rules, ranging from 626 to 1081 cases and from 8.14 to 10.04 per 100,000 patient-years. The proportion of OHCA patients meeting both TOR criteria and extended kidney criteria ranged from 67.8% to 73.6% of total cases of OHCA who did not achieve sustained ROSC.

Conclusion:
Our findings demonstrate that the implementation of a uDCD program, in cases where TOR rules indicate no chance of survival, has the potential to significantly increase the pool of potential organ donors.
Abstract 15800: Evaluating the Correlation Between Right Ventricular Outflow Tract Dimensions and Arrhythmia Risk Following Self-Expanding Transcatheter Pulmonary Valve Replacement
Authors: Soszyn Natalie , Yuen Gabriel , Rodriguez Franco Salvador A , Morgan Gareth J , Zablah Jenny
Published: December 2023

Introduction:
The introduction of self-expanding valves has allowed for an expanded range of patients who can be treated with transcutaneous pulmonary valve replacement (TPVR). Though major complications are rare, ventricular tachycardia has been reported following self-expanding valve placement prompting investigation of potential risk factors.

Hypothesis:
Significant variation in valve dimensions within the right ventricular outflow tract (RVOT) throughout the cardiac cycle is postulated as a cause for increased arrhythmia risk. We hypothesized that greater dynamic variation of the valve in the RVOT correlates to higher ventricular arrythmia risk.

Methods:
A single center review was performed of patients who underwent TPVR with either Harmony TPV or Alterra Pre-stent with subsequent placement of 29mm Sapien valve between 2019 and 2023. Using post-procedural 3D rotational angiography, minimum (systole) and maximum (diastole) diameters (mm), perimeter (mm) and cross-sectional area (mm
2
) of the valve frame were measured in two locations: closest to the branch pulmonary artery bifurcation and the RV cavity.

Results:
Twenty-eight patients were included (14 Harmony TPV, 14 Alterra). Higher frequency of ventricular arrythmia was seen in patients with congenital pulmonary stenosis (
p
=0.004). Higher ventricular arrythmia rate was associated with larger diastolic diameter (34.1 vs 33.2mm,
p
=0.04), mean perimeter (118.3 vs 108.6mm,
p
=0.03) and area (1124.5 vs 926.2mm
2
,
p
=0.03) of the valve frame closest to the RV cavity.

Conclusions:
Increased movement of the valve frame close to the RV cavity may correlate with a higher ventricular arrythmia risk due to increased contact with the native RVOT throughout the cardiac cycle. Future studies should focus on more accurate, mathematical methodology to better understand whether the complex interaction between self-expanding valves and the native RVOT is a determinant for post-procedural ventricular arrythmia.