bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12157: 4d Flow Mri Demonstrates Hemodynamic Normalization After Coarctation Repair in Pediatric Patients
Authors: Berhane Haben , Shahid Labib , Rice James , Rigsby Cynthia K , Robinson Joshua D , Griffin Lindsay , Roldan Alzate Alejandro , Markl Michael
Published: June 2023

Background:
Coarctation of the aorta (COA) is a focal aortic narrowing, and intervention is required for patients with severe hemodynamic impairment. Following intervention, patients remain at risk for long-term re-coarctation. We used 4D flow MRI to assess aortic hemodynamics pre- and post- COA repair in children compared to age matched healthy controls.

Methods:
Aortic 4D flow MRI was performed in 5 pediatric COA patients (baseline age 6-14 yrs, 1F) pre- and post COA repair (4 native COA, 1 re-intervention) and 5 age-matched controls (ages 9-17 yrs, 2 female). Peak systolic velocities were quantified with velocity maximum intensity projections (MIP) ROIs in the ascending aorta (AAo), aortic arch, distal to the coarctation, and descending aorta (DAo) (Figure 1A). For flow quantification, nine 2D planes were placed along the aorta. Regional net flow was determined by averaging the 2D plane flows by region. The ratio between DAo to AAo (DAo/AAo) net flow was used to assess collateral flow.

Results:
Velocities were generally higher and more consistent across the aorta following surgery (Figure 1A). Plots highlighting changes in DAo/AAo flow ratio are shown in Figure 1B. Compared to controls, DAo/AAo flow ratio was significantly lower prior to COA repair (0.38±0.11 vs 0.61±0.05, p = 0.0004), indicating flow obstruction at the COA and presence of substantial collateral flow. Post COA repair DAo/AAo flow ratio was similar compared to age matched controls (0.59±0.06 vs 0.61±0.05, p = 0.51), indicating normalization of aortic flow. Patient 2, who underwent COA repair via stent placement showed the greatest improvement and normalization of flow consistency (DAo/AAo) across the aorta after intervention.

Conclusion:
A
ortic 4D flow MRI shows normalization of aortic flow velocities, decreased collateral flow following COA repair, and has potential for long term surveillance and quantification of pre- and post-COA repair hemodynamic changes in children.
Abstract 12160: Sex Differences in Outcomes of Percutaneous Coronary Intervention in Octogenarians: A Retrospective Cohort Study From National Inpatient Sample 2016-2019
Authors: Baral Nischit , Santos Volgman Annabelle S , parajuli prem , Adhikari Govinda , Bashyal Krishna , Ojha Niranjan , Saleh Hassan , Balmuri Shravya , Kunadi Arvind , Abdelazeem Basel , Arida Abdul , Obeidat Islam , Seri Amith Reddy , Kambalapalli Soumya , Paul Timir K
Published: June 2023

Introduction:
The role of sex-based differences in the outcomes after principal percutaneous coronary intervention (PCI) in octogenarians is not well studied.

Hypothesis:
There are no differences in outcomes of PCI in octogenarians based on sex.

Methods and Results:
From 2016 to 2019, 37,147 hospitalizations (unweighted sample) for principal PCI procedures were identified. Among the principal PCI procedures performed, 44.9% (n = 16,660) were performed in females, and 55.2% (n = 20,487) in males (p < 0.001), 82.4% in Whites, 5.4% in Blacks, 6.4% in Hispanics, and 2.6% in Asians. 20,986 (56.5%) principal PCI hospitalizations had a Charlson comorbidity index (CCI) of three or higher. The mean age for Octogenarians was 83.6 ± 2.7 years. Compared to males, the females were slightly older (mean age: 83.8 vs. 83.5; p < 0.001), had higher prevalence of diabetes mellitus (20.5% vs 18%, p<0.001) and lower Charlson comorbidity index (CCI) of three or higher (53.6% vs. 58.9%, p <0.001). Females had higher incidence of cardiogenic shock (4.9% vs 4.2%, p=0.002), higher in-hospital mortality (4% vs 3%, p<0.001) and longer length of stay (LOS) (4.4 days vs 4.1 days, p<0.001). Multivariate regression analysis showed that, compared to males, females had a significantly higher odds of in-hospital mortality (aOR: 1.23; 95% CI: 1.10, 1.37; p <0.001) and cardiogenic shock (aOR: 1.17; 95% CI: 1.06, 1.30; p=0.002) after controlling for age, race, hospital region, hospital teaching status, income, insurance provider, and CCI. From 2016-2019, in octogenarians, the annual incidence of principal PCI hospitalizations increased from 127 per 100,000 hospitalizations in 2016 to 137 per 100,000 hospitalizations in 2019, p<0.001.

Conclusions:
The incidence of PCI done in octogenarians is rising every year. Females have an increased likelihood of in-hospital mortality, longer LOS, and cardiogenic shock.
Abstract 12187: Transcatheter versus Surgical Aortic Valve Replacement With Concurrent Coronary Revascularization: A Systematic Review and Meta-Analysis
Authors: Sakurai Yosuke , Yokoyama Yujiro , Fukuhara Shinichi , Takagi Hisato , Kuno Toshiki
Published: June 2023

Objective:
This meta-analysis aimed to evaluate outcomes of transcatheter aortic valve replacement (TAVR) with percutaneous coronary intervention (PCI) versus surgical aortic valve replacement (SAVR) with coronary artery bypass grafting (CABG).

Methods:
MEDLINE and EMBASE were searched through November 2021 to identify studies comparing TAVR+PCI and SAVR+CABG for severe aortic stenosis with concurrent coronary artery disease. Outcomes of interest were long-term all-cause mortality, repeat coronary intervention, rehospitalization, myocardial infarction, and stroke during follow-up, and 30-day periprocedural outcomes.

Results:
Two randomized controlled trials and six observational studies including a total of 104,220 patients (TAVR+PCI, n = 5,004; SAVR+CABG, n = 99,226) were included. Median follow-up periods ranged from one to three years. TAVR+PCI was associated with higher all-cause mortality and coronary reintervention during follow-up period (Hazard Ratio [HR], 1.35; 95% confidence interval [CI], 1.11-1.65; p = 0.003, HR, 4.14; 95% CI, 1.74-9.86; p = 0.001, respectively), 30-day permanent pacemaker implantation rate (Odds Ratio [OR], 3.79; 95% CI, 1.61-8.95; p = 0.002), and periprocedural vascular complications (OR 6.97; 95% CI, 1.85-26.30; p = 0.004). In contrast, TAVR+PCI was associated with a lower rate of 30-day acute kidney injury (OR, 0.32; 95% CI, 0.20-0.50; p = 0.0001). Rehospitalization, myocardial infarction, stroke during follow-up, and other periprocedural outcomes including 30-day mortality were similar in both groups.

Conclusions:
In patients with severe aortic stenosis and coronary artery disease, TAVR+PCI was associated with higher all-cause mortality at follow-up compared with SAVR+CABG. Heart team approach to assess TAVR candidacy remains imperative.
Abstract 12195: Accurate Detection of Lead Malfunction Based on Ekg-Derived Bipolar Pacing Stimulus Amplitude
Authors: Pelling Mary , Ibrahim Rand , El-Chami Mikhael F , Lloyd Michael S
Published: June 2023

Introduction:
The increasing prevalence of pacemaker lead noise indicating insulation breach has previously been described. Unfortunately, early detection is neither predictable nor accurate by traditional measurements. “Pseudo-unipolarization” of bipolar pacing stimuli as observed from routine 12-lead EKG due to current leak holds promise as a means of detecting insulation breaches. We sought to characterize this EKG finding to better detect lead malfunction.

Methods:
138 patients who received transvenous lead implantations with pacing noted on EKG at time of implant (control group, n=50) or after time of known malfunction (malfunction group, n=88) were included. The highest amplitude (any of 12-leads on standard EKG, 10mm/mV, GE Marquette) of the bipolar pacing stimulus on EKG was recorded. Chi-squared analysis was used to compare categorical variables and independent t-test was applied for continuous values. An ROC curve for maximum EKG bipolar pacing stimulus amplitude was generated for prediction of lead functional status (normal versus malfunction).

Results:
The cohort (49% females, 34% non-white) had an average age of 67 ± 16 years at implant. Malfunction was chiefly identified by lead noise on routine interrogation, consisting of 61% RA and 39% RV leads with mean pacing output 2.74V at 0.5ms. Mean time to malfunction was 6 ± 4 years post implant. There was significant difference in EKG bipolar stimulus amplitudes at time of failure (15.06 ± 13.533mm, p<0.01) compared to those of normal leads (mean=2.54 ± 1.265mm), but no significant difference in pacing output. ROC curve for the prediction of lead malfunction based on EKG amplitude displayed area under curve=0.93 (95% CI [0.891, 0.969]). Selecting an EKG stimulus amplitude cut-off at 3.5mm for the prediction of lead malfunction demonstrated a sensitivity of 86.4% and a specificity of 76%.

Conclusion:
The amplitude of a bipolar pacing stimulus on EKG is significantly different among normal functioning leads and those with known malfunction due to insulation breach. We found reasonably good performance of this derived measure at distinguishing among the two groups using a cutoff of 3.5mm for EKG stimulus amplitude. A larger prospective dataset is needed to validate a reliable threshold point.
Abstract 12197: Causes of Death in Patients With Symptomatic Peripheral Artery Disease After Lower Extremity Revascularization: Insights From Voyager Pad
Authors: Canonico Mario Enrico , Capell Warren , Anand Sonia S , Patel Manesh R , Debus Eike Sebastian , Nehler Mark , Hess Connie , Hsia Judith A , Muehlhofer Eva , Haskell Lloyd P , Berkowitz Scott D , Bauersachs Rupert , Bonaca Marc P
Published: June 2023

Background:
In trials of patients with coronary artery disease (CAD), unknown deaths (e.g. out of hospital) are often categorized as sudden/presumed cardiovascular (CV) based on observations that recurrent coronary events are a major cause of mortality. Such conventions are applied broadly to CV trials, including those in peripheral artery disease (PAD). Recent trials in patients selected on the basis symptomatic PAD, such as EUCLID trial, report that only ~1/3 have known CAD. Therefore, understanding the causes of death in patients in trials of symptomatic PAD may help elucidate whether different conventions should be considered.

Hypothesis and Methods:
VOYAGER PAD enrolled patients with symptomatic PAD after lower extremity revascularization. Source documents were collected for all deaths and cause was adjudicated by an independent blinded CEC using accepted CV trial conventions for those dying out of hospital. For this post-hoc analysis, source documents were re-reviewed to provide further details regarding specific causes of deaths.

Results:
6564 patients were randomized and followed for a median of 28 months. A total of 637 deaths occurred, and of these, 35% were CV, 22% were unknown (e.g. out of hospital, sudden deaths), and 43% were non-CV. Of the CV deaths, 40% (14% of all deaths) were atherothrombotic (e.g. acute MI, stroke, PE), while 60% (21% of all deaths) were not atherothrombotic (e.g. heart failure, shock). Deaths due to cancer (17%) and infection (15%) were more frequent than atherothrombotic deaths.

Conclusions:
Patients recruited into trials for symptomatic PAD die of diverse causes. Atherothrombosis caused a minority of deaths, while heart failure, cancer, and infection are as or more frequent. These observations suggest that causes of death differ in populations selected on the basis of PAD versus CAD and that assumptions underlying categorization of deaths of unknown etiology should be carefully considered in these distinct populations.
Abstract 122: The Impact Of The Covid-19 Pandemic On The Incidence Of Ems Treated Out-of-hospital Cardiac Arrest Patients And The Incidence Of Bystander Cardiopulmonary Resuscitation (cpr); A World-wide Perspective
Authors: Tjelmeland Ingvild B , Kramer-Johansen Jo , Wnent Jan , Graesner Jan-Thorsten
Published: June 2023

Introduction:
Survival after OHCA is dependent on early recognition, early cardiopulmonary resuscitation (CPR) and early defibrillation. The purpose of CPR is to maintain some blood flow until the arrival of the emergency medical services (EMS). Our concern was that the Covid-19 pandemic would have a negative effect on the number of patients who got CPR before EMS arrival. The aim of this study is to compare the incidence of EMS treated patients and the incidence of bystander CPR during the pandemic with data from before the pandemic.

Method:
This is a retrospective cohort study using data from existing cardiac arrest registries. The participants are from 24 countries, where Australia and USA have four regions each, resulting in 30 individual participants. All participating registries share aggregated data from 2017 to 2020, and results from before and after lockdown is compared. Poisson regression was used to look at differences.

Results:
Preliminary results from 14 registries show that the incidence of EMS treated patients per 100.000 inhabitants was statistically increased in five registries, decreased in three registries, and had no statistical difference in six registries. The incidence of bystander CPR was statistically higher after lockdown in five registries, decreased in one registry and was unchanged in eight registries. Four regions had an increase in both incidence of EMS treated patients and the incidence of bystander CPR.

Conclusion:
Bystanders willingness to perform CPR seems unchanged by the Covid-19 pandemic.
Abstract 12210: Safety and Efficacy of Transcatheter Aortic Valve Replacement With Continuation vs Interruption of Peri-Procedural Anticoagulation: A Meta-Analysis
Authors: Agarwal Siddharth , Bansal Agam , Akhtar Khawaja , khan Jehanzeb , Anwaar Muhammad Faraz , Maheshwari Supriya , Garg Nikita , Baber Usman
Published: June 2023

Introduction:
Approximately 33% of patients undergoing transcatheter aortic valve replacement (TAVR) have an indication for long-term anticoagulation. In clinical routine, anticoagulation is often discontinued 2 to 4 days before TAVR. The purpose of this meta-analysis was to compare the safety and efficacy of TAVR in patients with per-procedural continuation vs interruption of anticoagulation.

Methods:
An electronic search was performed using PubMed and Ovid Medline from inception to May 2022. The primary outcome of interest was life-threatening or major bleeding. The secondary outcomes were all-cause mortality, stroke, vascular complications, need for blood transfusion, and closure device failure.

Results:
Three observational studies were included in our final analysis which consisted of 2,286 patients, with anticoagulation being continued in 1,069 patients and interrupted in 1,217 patients. Although, there was no significant difference in our primary outcome of life-threatening or major bleeding between both groups, there was a trend toward decreased risk of bleeding in patients who were continued on anticoagulation (RR: 0.81; CI: 0.65 to 1.0; I
2
: 0%, p=0.05). There was a significantly lower risk of stroke (RR: 0.55; CI: 0.35 to 0.88; I
2
: 0%, p=0.01) and need for blood transfusion (RR: 0.72; CI: 0.59 to 0.87; I
2
: 0%, p<0.01) in patients who were continued on anticoagulation as compared to those in whom anticoagulation was interrupted. There was no significant difference in the all-cause mortality (RR: 0.76; CI: 0.49 to 1.19; I
2
: 10%, p=0.24), major vascular complications (RR: 0.86; CI: 0.68 to 1.09; I
2
: 0%, p=0.22), or closure device failure (RR: 0.90; CI: 0.51 to 1.59; I
2
: 0%, p=0.72) between both the cohorts.

Conclusions:
In a patient undergoing TAVR who requires long-term anticoagulation, continuing anticoagulation is superior to interrupting anticoagulation in reducing the risk of stroke without any increase in life-threatening or major bleeding.
Abstract 12212: Heart Failure With Preserved Ejection Fraction: A Cardiologist Disorder or a Nephrologist Problem? Analysis From a Largely Hispanic Population
Authors: Patel Rahul N , Sharma Akash , Ahuja Roma , Tran Nghia , Garza Aliseiya , Bansal Shweta
Published: June 2023

Introduction:
Heart failure with preserved ejection fraction (HFpEF) has been recognized as a multisystem process and chronic kidney disease (CKD) plays a central role in this paradigm. However, racial/ethnic variability and prevalence of CKD are not well described.

Hypothesis:
We hypothesize that the South Texas Hispanic patient population has a different phenotypic expression of HFpEF compared to the largely White population in the EMPEROR-Preserved trial.

Methods:
Consecutive HFpEF patients (total n=204) were identified from a HF population screened for a clinical trial from 2019-2020 (n=188) and inpatients with HF exacerbation during 2021 (n=16) at University Hospital. HFpEF was defined as symptomatic HF with left ventricular ejection fraction (LVEF) >40% on Echo. Clinical and lab variables were collected ±1 year from Echo date. Race/ethnicity was self-reported. CKD was identified from the problem list. Rates were compared with EMEPROR-Preserved trial’s HFpEF population which was largely White.

Results:
Of 204 HFpEF patients, 9 were Black, 14 were from other races, and due to small size were excluded from the analysis. Majority of the study population were Hispanics (130 of 181, 72%). LVEF was 40-50% in 31% of the study population.
Table 1
demonstrates characteristics by EMPEROR population, and Hispanics and non-Hispanic Whites (NHW) in our analysis. Of significance, our population was younger, had DM2, CAD, CKD, and obesity at higher rates, and AFib and BNP at lower rates as compared to EMPEROR population. The differences in Hispanics and NHW were unremarkable except more HTN and lower eGFR in Hispanics.

Conclusions:
Hispanic patients with HFpEF have more frequent diabetes, CKD and CAD as compared to White population in EMPEROR-Preserved trial. In context of this observation and recent success of newer agents as empagliflozin, a multispecialty integrative approach is strongly warranted for management of HFpEF patient population.
Abstract 12235: Contribution of Individual-Level Factors to Racial and Ethnic Differences in Cardiovascular Health in the United States Population
Authors: Shah Nilay S , Huang Xiaoning , Petito Lucia , Bancks Michael , Ning Hongyan , Cameron Natalie , Kershaw Kiarri N , Kandula Namratha , Carnethon Mercedes R , Lloyd-Jones Donald , Khan Sadiya S
Published: June 2023

Introduction:
Individual-level factors across several domains underlie racial and ethnic differences in cardiovascular health (CVH). Quantifying the contributions of these determinants to racial and ethnic differences in CVH may inform targeted strategies to mitigate inequities.

Methods:
In data from NHANES 2011-2018, we calculated mean CVH score (range 0-14; defined by AHA’s Life’s Simple 7 metrics) among US adults ≥20 years. We applied Kitagawa-Blinder-Oaxaca decomposition to quantify the contributions of education, income, food security, marital status, health insurance, place of birth (US vs. foreign born), and depression to racial and ethnic differences in CVH.

Results:
Among 16,172 participants representing 255 million US adults, 41% were non-Hispanic (NH) White, 23% NH Black, 24% Hispanic, and 12% NH Asian. Among males, mean (SE) CVH score was 7.58 (2.3) in NH White, 7.48 (2.4) in NH Black, 7.45 (2.3) in Hispanic, and 8.71 (2.2) in NH Asian adults. Education explained the largest component of CVH differences in males (if education were similar to NH White, CVH score would be 0.23 [0.03] points higher in NH Black, 0.36 [0.04] points higher in Hispanic, and 0.24 [0.04] points lower in NH Asian, p<0.05; Figure A). Among females, mean (SE) CVH score was 8.00 (2.5) in NH White, 7.43 (2.3) in NH Black, 8.03 (2.4) in Hispanic, and 9.34 (2.1) in NH Asian adults. Education explained the largest component of CVH difference in NH Black females (if education were similar to NH White, CVH score would be 0.17 [0.03] points higher in NH Black, p<0.05; Figure B). Place of birth explained the largest component of CVH difference in Hispanic and NH Asian females (if place of birth were similar to NH White, CVH score would be 0.36 [0.07] points lower and 0.49 [0.16] points lower, respectively, p<0.05).

Conclusion:
Education and place of birth confer the largest contributions to the net difference in mean CVH score among racial and ethnic groups in the US.
Abstract 12273: Crispr-Mutation of the Na
+
-k
+
Pump β1-Subunit Protects Against Cardiac Fibrosis and Heart Failure in Mice
Authors: Wu Di , Genetzakis Elijah , Ng Hooi H , Barsha Giannie , Besnier Marie , Bubb Kristen , Figtree Gemma A
Published: June 2023

Introduction:
The Na+-K+ pump controls translocation of Na+ and K+ across the cell membrane which indirectly affects heart muscle contraction. Glutathionylation of the Na+-K+ pump’s β1 subunit (NKβ1) is a reversible post-translational oxidative modification, where a glutathione adduct forms a disulphide bond with the cysteine residue at site 45, leading to a reduction in pump activity. Using CRISPR/Cas9 technology, we created a transgenic mouse line (CRISPR-β1) that has a mutation in cysteine to serine at site 45 on NKβ1, causing insensitivity to β1-GSS.

Hypothesis:
We hypothesize that a mutation of the β1-GSS can inhibit transverse aortic constriction (TAC)-induced cardiac fibrosis.

Methods and Results:
TAC was induced in both the wild-type (WT) and CRISPR-NKβ1 mutated mice (CRISPR-β1) over a period of four weeks. Gene sequencing showed that cysteine 45 was replaced by serine, and immunoprecipitation of the free cysteine demonstrated that cysteine 45 was mutated in the β1 subunit of the CRISPR-β1 mice hearts. TAC significantly reduced cardiac function in the WT but not the CRISPR-β1 mice (ejection fraction: WT TAC: 36.24% ± 3.49%; CRISPR-β1 TAC: 57.5% ± 3.41%). Similarly, we found that the CRISPR-β1 mice were protected from cardiac hypertrophy, as evidenced by a significant reduction in cardiomyocytes size (WT TAC: 452.1 μm2 ± 30.74 μm2 ; CRISPR-β1 TAC: 271.1 μm
2
± 11.0 μm
2
). TAC significantly increased interstitial and perivascular fibrosis in the left ventricles of WT but not the CRISPR-β1 mice (interstitial: WT TAC: 18.4% ± 1.96%; CRISPR-β1 TAC: 5.2% ± 1.62%, perivascular: WT TAC: 42.6% ± 4.5%; CRISPR-β1 TAC: 22.01% ± 1.6%). Cardioprotective effects observed in the CRISPR-β1 mice were at least in part attributed to a significant reduction in the expression of ANP, BNP, Tgfb1, Fn1 and Ctgf genes.

Conclusions:
Our data indicate that CRISPR mutation of the Na+-K+ pump’s β1 subunit prevents the development of cardiac fibrosis and heart failure in a TAC-induced mouse model.
Abstract 12277: Impact of Telemedicine New Patient Visits on Total Visit Utilization at an Academic Cardiovascular Center: An Instrumental Variable Analysis
Authors: Kalwani Neil M , Koos Harrison , Oesterle Anica , Kohn Emily V , Parameswaran Vijaya , Qureshi Lubna , Dash Rajesh , Scheinker David , Rodriguez Fatima
Published: June 2023

Introduction:
Telemedicine use has increased, but little is known about the impact of telemedicine on downstream healthcare utilization. We sought to determine the effect of conducting new patient visits (NPVs) through telemedicine on the number of follow-up visits for common cardiovascular conditions.

Methods:
We extracted data for all visits at an academic cardiovascular center from Jan 2019 to Feb 2022. We evaluated the effect of telemedicine vs in-person NPVs on total follow-up visits within 6 months for patients seen for 8 common primary diagnoses between Jun 2020 and Aug 2021. We utilized variation in the rate of telemedicine use among clinicians as an instrumental variable, adjusting for patient characteristics, diagnosis, subspecialty, and site. We used two-stage least squares (2SLS) and instrumental causal forest (ICF) models.

Results:
There were 4,856 NPVs and 3,594 follow-up visits. NPVs were delivered by 120 clinicians with 58.8% provided by telemedicine (range 0-100% across clinicians). There was no association between the average number of follow-up visits before Mar 2020 and subsequent clinician telemedicine adoption. In 2SLS analysis, there was no significant overall effect of delivering NPVs through telemedicine on the number of follow-up visits within 6 months (-0.029 visits per patient, 95% CI -0.15, 0.089). The ICF analysis similarly showed no significant overall effect of telemedicine NPVs on the number of follow-up visits. In 2SLS subgroup analyses, the effect of telemedicine NPVs differed across diagnoses (Figure).

Conclusions:
At an academic cardiovascular center, use of telemedicine NPVs for several common diagnoses did not affect the total number of follow-up visits within 6 months. Telemedicine NPVs can successfully replace in-person visits though their impact on total visits may differ across cardiovascular conditions. Future research should evaluate the effect of visit modality on other domains of care utilization and outcomes.
Abstract 12293: Retinoic Acid Signaling Regulates Smooth Muscle Cell Phenotypic Switching in Atherosclerosis Through Epigenetic Modulation of Gene Expression
Authors: Pan Huize , Xue Chenyi , Cui Jian , Ross Leila S , Ho Sebastian E , Reilly Muredach P
Published: June 2023

Background:
Smooth muscle cells (SMCs) substantially contribute to atherosclerosis through “phenotypic switching.” Our previous work identified an intermediate SMC-derived cell type, termed “SEM” cells, which was multipotent and activated in inflammatory response. Activation of retinoic acid (RA) signaling by all-trans retinoic acid (ATRA) attenuated atherosclerosis in mice coincident with dramatic suppression of SEM cell formation from SMCs. However, the regulatory mechanisms by which RA signaling modulates SMC transition to SEM cells are largely unknown.

Methods:
We employed molecular and cell biology techniques, SMC-linage tracing and atheroprone mouse models, and next-generation sequencing (e.g., RNA-seq, ChIP-seq) to reveal how RA signaling modulates SMC transition to SEM cells.

Results:
Activation of RA signaling with ATRA significantly reduced SEM cells in established atherosclerosis, as well as downregulated the expression of SEM cell marker genes (e.g.,
Ly6a
,
Ly6c1
) and repressed inflammatory response in
ex vivo
SEM cells, whereas inhibition of the signaling with antagonist, BMS49334, showed opposite results. RARα occupied the promoter regions of SEM cell marker genes, and ATRA treatment significantly increased the enrichment of NCOR1 at promoters of these genes. These findings suggest that RA signaling suppresses SMC transition to SEM cells via directly repressing the expression of SEM cell marker genes. Furthermore, we found EZH2, one of the subunits of PRC2, physically interacted with RARα in SMCs and occupied the promoters of SEM cell marker genes, and its methyltransferase activity at the promoter regions was responsible for the repression of SEM cell maker genes. Moreover, activation of RA signaling inhibited SEM cell inflammatory response through LXR-mediated suppression of a series of inflammatory genes. Finally, multiple epigenetic signatures (e.g., H3K27me3, H3K27ac, H3K4me3, etc.) at TSS of SEM cell marker genes and inflammatory genes were extensively altered in response to the activation of RA signaling.

Conclusions:
Our findings indicate that RA signaling modulates maintenance of SEM cell identity and inflammatory function in atherosclerosis by epigenetic regulation of gene expression.
Abstract 12294: Gut Microbial Features Associated With Sedentary Time But Not Physical Activity: Results From the Hispanic Community Health Study / Study of Latinos (HCHS/SOL)
Authors: Moon Jee-Young , Lin Juan , Sotres-Alvarez Daniela , Schneiderman Neil , Daviglus Martha L , Thyagarajan Bharat , Rodriguez Carlos , Qi Qibin , Burk Robert , Ramachandran Vasan S , Mossavar-Rahmani Yasmin , Kaplan Robert
Published: June 2023

Introduction:
Modest experimental and human evidence implicate a role for physical activity or sedentary lifestyle in the perturbation of the gut microbiome, yet large human studies are lacking.

Methods:
This study included 1846 US Hispanic/Latino adults without diabetes aged 23-82 years (mean age 48 years, 49% women) with gut microbiome data by shotgun sequencing of stools and accelerometer-measured moderate-to-vigorous physical activity (MVPA) and sedentary time from the HCHS/SOL population based cohort (2014-2017). We examined associations of MVPA and sedentary time with gut microbial features - Bray-Curtis dissimilarity by PERMANOVA, and alpha diversity and centered log ratio transformed relative abundance of species and KEGG pathway modules by a linear regression accounting for the complex survey design.

Results:
Prolonged sedentary time was associated with higher Shannon index (0.03 per 1 hr of sedentary time, SE=0.02, P=0.077) and Bray-Curtis dissimilarity (R
2
=0.32%, P<0.001), adjusting for age and sex, but MVPA showed no association. Among 197 species with at least 0.01% average relative abundance, sedentary time was positively associated with 30 species including 8
Bacteroides
species,
Alistipes putredinis
and
finegoldii
, and inversely with 19 species including 7
Prevotella
species,
Roseburia faecis
, and
Bifidobacterium adolescentis
(FDR <.1, Figure), whereas no species was associated with MVPA. A KEGG pathway module analysis suggested elevated methane metabolism, bacterial secretion, and carbon fixation with higher sedentary time (P<.05) but none after FDR correction (all FDR>.1). Positive associations were observed between MVPA with D-glucuronate degradation and semi-phosphorylative Entner-Doudoroff pathway (gluconate → glycerate-3P, found in halophilic
euryachaea
and
Clostridium
species) (P<.05 but FDR>.1).

Conclusions:
We observed a perturbed overall gut microbiome and relative abundance of species with sedentary time.
Abstract 12299: Impact of Diabetes Mellitus on Clinical Outcomes in Patients With Minimal and Intermediate Coronary Artery Disease Diagnosed by Coronary Ct Angiography
Authors: Cho Sung Woo , Kim Dong-Gil , Hwang Ji-Won , Doh Joon-Hyung , Kwak Jae-Jin , Namgung June , Lee Sung Yun , Kwon Sung Uk
Published: June 2023

Introduction:
Diabetes mellitus (DM) is the most important risk factor for coronary artery disease (CAD) progression and prognosis. The DM patients with normal coronary artery on coronary CT angiography (CCTA) had good prognosis, however the prognosis of minimal and intermediate CAD was not fully elucidated. The aim of this study was to investigate the impact of DM on clinical outcomes in patients with minimal and intermediate CAD diagnosed by CCTA.

Methods:
A total of 6014 patients underwent CCTA were prospectively enrolled and the 1126 patients with minimal and intermediate CAD were analyzed. Patients were categorized according to maximal severity of coronary artery stenosis: minimal CAD (31 to 50%) and intermediate CAD (51 to 70%). The primary outcome was major adverse cardiac events (MACE) including all-cause death, non-fatal myocardial infarction, coronary revascularization, or cardiac hospitalization.

Results:
Nine hundred eighty-five patients had minimal CAD and 141 patients had intermediate CAD. The DM patients were 307 (31.2%) in the minimal CAD group and 52 (36.9%) in the intermediate CAD group. During the follow-up period (median 18.9 months [interquartile range: 7.8 to 34.6 months]), there is no significant difference of the risk of MACE between the non-DM and DM patients in the minimal CAD group (26.9% vs. 32.8%; adjusted hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.74-1.49;
p
=0.79). However, compared with the non-DM patients, the DM patients significantly increased the risk of MACE in the intermediate CAD group (36.5% vs. 63.2%; adjusted HR, 2.37; 95% CI, 1.18-4.77;
p
=0.02).

Conclusions:
The prognosis of the DM patients was similar with the non-DM patients in the minimal CAD group. However, the DM patients had worse clinical outcomes compared with the non-DM patients in the intermediate CAD group.
Abstract 12311: The Impact of Ejection Fraction on Major Adverse Limb Events After Lower Extremity Revascularization
Authors: Jamil Yasser , Huttler Joshua , Alameddine Dana , Zhuo Haoran , Mena-Hurtado Carlos , Velazquez Eric J , Guzman Raul J , Ochoa Chaar Cassius Iyad I
Published: June 2023

Objective:
Peripheral arterial disease (PAD) is commonly associated with cardiac disease and echocardiography is frequently performed prior to lower extremity revascularization (LER). However, the incidence of various echocardiographic findings and their impact on the outcomes of LER have not been well studied.

Hypothesis:
Low ejection fraction (EF) ≤ 40% is associated with increased major adverse limb events (MALE) after LER.

Methods:
The electronic records of patients undergoing LER in a single center were reviewed. Patients were divided based on the presence or absence of reduced EF ≤ 40%. Patient, echocardiographic, and procedural characteristics were compared as well as outcomes.

Results:
A total of 1,034 patients (N=130, 12.5% with EF≤ 40%) underwent LER. Patients with reduced EF were more likely to be males, with coronary artery disease and heart failure. On echocardiography, patients with reduced EF had significantly higher mean right ventricular pressure and were more likely to have diastolic dysfunction. Moderate to severe regurgitation affecting the mitral and tricuspid valves were significantly higher in patients with reduced EF. There was no difference in indication but patients with reduced EF were more likely to be treated with endovascular procedures. Perioperatively, patients with reduced EF were more likely to develop myocardial infarction. (Table) There was no difference in MALE or major amputation between the 2 groups but MALE-free survival was significantly lower for patients with EF≤ 40%. (Figure).

Conclusion:
Reduced EF is associated with decreased survival of patients with PAD after LER but does not seem to significantly impact MALE.
Abstract 12313: Uncovering Functional and Structural Remodeling Progression of Persistent Atrial Fibrillation Over Time in a Rapid Atrial Pacing Canine Model - New Mechanistic Insights in Persistent Atrial Fibrillation
Authors: Rottmann Markus , Yoo Shin , Pfenniger Anna , Knight Bradley P , Passman Rod , Lee Daniel C , Arora Rishi
Published: June 2023

Introduction:
The specific underlying persistent AF mechanisms are complex, and their development and remodeling processes over time are still not well understood.

Hypothesis:
We hypothesized that continuous rapid atrial pacing (RAP) in dogs induces persistent AF by affecting electrogram measures, fibrosis and oxidative stress (OS).

Methods:
AF was induced in 15 dogs (25-35 kg, 1 year) by RAP (3-14 weeks RAP, 600 beats/min), and 7 control dogs were used. We performed high-resolution epicardial mapping in 15 dogs and 8 controls using a high-density epicardial mapping plaque (6 regions, 130 electrodes, electrode distance 2.5mm) (
Figure A
). We analyzed the electrogram measures cycle length (CL) and dominant frequency (DF) in the 6 atrial regions in the left (LA) and right atrium (RA). MRI native T1 mapping was performed using a 1.5T clinical scanner (Siemens Aera) in 7 persistent AF dogs and in 8 dogs at baseline in the posterior left atrium (PLA). We quantified in 6 atrial regions in both atria the oxidative stress (OS) levels as the ratio of oxidatively damaged nuclei against the total number in 8-OHdG staining in (N=36 samples in 6 animals) and the degree of dense fibro-fatty tissue in Masson’s trichrome stained tissue (N=24 in 4 animals) using Qupath in all 6 regions in both atria.

Results:
Rapid atrial pacing (RAP) weeks correlated with CL (R=0.6, P 0.05) in the PLA (
Figure B
). Native T1 signal intensity increased with RAP days (R=0.6, P 0.05) in the PLA (less than 142 pacing days) (
Figure C
). Highest degree of dense focal fibrosis/ fat was in the left atrial free wall (LAFW) (49+/-14%) and in the PLA (47+/-19%) (
Figure F
). OS levels, highest in the LAFW, lowest in the appendages increased with the degree fibrosis (R=0.6, P<0.05) and with decreasing cycle length (R=0.5, P<0.05) in all atrial regions (
Figure D,E,G,H,I
).

Conclusions:
Continuing persistent AF is associated with smaller CL, increasing fibrosis, and oxidative injury rapid atrial pacing time.
Abstract 12324: Biomarker Trends in Patients With Immune-Checkpoint Inhibitor Myocarditis
Authors: Vasbinder Alexi , Chen YeeAnn , Gradone Allison , Azam Tariq , Perry Daniel , Shadid Husam , Anderson Elizabeth , Catalan Tonimarie , Blakely Pennelope , Adie Sarah , Pogue Kristen , Leja Monika , Yentz Sarah , Schneider Bryan , Fecher Leslie , Lao Christopher D , Hayek Salim
Published: June 2023

Introduction:
Immune checkpoint inhibitors (ICIs) are associated with myocarditis; however, there is no consensus on strategies to identify or monitor for myocarditis. We sought to characterize longitudinal biomarkers in patients receiving ICIs.

Methods:
We conducted an observational cohort study of adult (≥18 years) patients who had received at least one dose of single or dual ICI at Michigan Medicine between June 2014 - December 2021. Patients were identified as having myocarditis if a clinical diagnosis was noted in the medical record by the cardiovascular consult team. Laboratory values (i.e., high-sensitivity troponin-T [hsTnT], aspartate transaminase [AST], alanine transaminase [ALT], lactate dehydrogenase [LDH], and creatinine phosphokinase [CPK]) were collected from medical records for 12 months after beginning ICI.

Results:
In 2,606 patients (mean (SD) age 64 (13) years; 60.8% male), 27 (1.0%) developed myocarditis at a median (IQR) time of 28 (18,40) days after starting ICIs. At diagnosis, most patients with myocarditis had a non-cardiac immune-related adverse event (88.9%) and an elevated ALT (88.9%), AST (85.2%), CPK (88.9%), and LDH (92.6%). All patients with myocarditis had an elevated hsTnT. Compared to patients without myocarditis, patients with myocarditis had significant elevations in ALT, AST, CPK, and LDH after starting ICIs (all P<0.001) (Figure). In patients with myocarditis, average concentrations of AST and ALT remained elevated at 12 months, whereas CPK peaked at 1 month then rapidly declined. Average concentrations of all biomarkers in patients without myocarditis were in the normal range. CPK values greater than the upper limit of normal had a sensitivity and specificity of detecting myocarditis of 99% and 23%, respectively.

Conclusions:
Myocarditis rarely occurs in the absence of other immune-related adverse events. Elevated AST, ALT and CPK should prompt measuring hs-TnT and initiating further evaluation for ICI myocarditis.
Abstract 12326: Heart Rate Variability According to Ambulatory Glucose Profile in Patients With Diabetes Mellitus
Authors: Im Sung I
Published: June 2023

Introduction:
Autonomic neuropathy commonly arises as a long-term complication in diabetes mellitus (DM) and can be diagnosed from heart rate variability (HRV), calculated from electrocardiogram (ECG) recordings.

Hypothesis:
There is limited data about HRV using real-time ECG and ambulatory glucose monitor in patients with diabetes mellitus

Methods:
Total of 43 patients (66.3±7.5 years) with DM underwent continuous real-time ECG monitor (225.7±107.3 hours) for HRV and ambulatory glucose monitor using remote monitoring system. And we compared HRV according to ambulatory glucose profile .

Results:
During the monitor, we checked total 15090 times of ECG and ambulatory glucose level simultaneously of all patients. Both time and frequency domain HRV were lower when the patients had poor controlled glucose level (>200mg/dL) as compared with normally controlled glucose levels (<200mg/dL) in Table. In addition, Heart rate and respiration rate increased according to real-time glucose level (P<0.001).

Conclusions:
Poor controlled glucose level was independently associated with lower HRV in patients with DM. This is further substantiated by independent continuous associations between real-time measures of hyperglycemia and lower HRV. These data strongly suggest that cardiac autonomic dysfunction can be caused by elevated blood sugar alone.
Abstract 12332: Comparative Cost-Effectiveness of Sacubitril-Valsartan, Dapagliflozin, and Empagliflozin in Heart Failure With Reduced Ejection Fraction
Authors: Parikh Neil U , Dixit Neal , Ziaeian Boback , Fonarow Gregg C
Published: June 2023

Introduction:
The 2022 American College of Cardiology/American Heart Association (ACC/AHA) guidelines established angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter-2 inhibitors as Class I therapies in heart failure with reduced ejection fraction (HFrEF). Previous analyses have demonstrated the cost-effectiveness of these drugs, but use of different methodologies limit comparison. The objective of this study was to use a singular model to compare the cost-effectiveness of these agents in HFrEF.

Methods:
A 2-state Markov model was developed to compare the incremental cost-effectiveness ratios of sacubitril-valsartan, dapagliflozin, and empagliflozin. The enalapril arm of the PARADIGM-HF trial served as the control. Data from the PARADIGM-HF, DAPA-HF, and EMPEROR-Reduced trials were used to simulate treatment with sacubitril-valsartan, dapagliflozin, and empagliflozin, respectively. The model used a lifetime time horizon from a United States healthcare perspective. All costs and quality-adjusted life years were discounted 3% annually. The primary outcome was the incremental cost-effectiveness ratio of each treatment compared to control.

Results:
The incremental cost-effectiveness ratios of sacubitril-valsartan, dapagliflozin, empagliflozin, were $74,111, $72,048, and $118,253, respectively. Figure 1 shows the incremental cost-effectiveness ratios and incremental quality-adjusted life years in the present analysis compared to previously published analyses.

Conclusions:
In a singular model of patients with HFrEF, sacubitril-valsartan, dapagliflozin, and empagliflozin all met the threshold for intermediate value ($50,000-$150,000 per quality-adjusted life year gained) set by the ACC/AHA.
Abstract 12336: Genetic Testing in a Population of Patients With End Stage Heart Failure — Too Little, Too Late?
Authors: Kamal Maani Z , Kang Jennifer , Peyster Eliot G , Owens Anjali T , Reza Nosheen
Published: June 2023

Introduction:
Nonischemic dilated cardiomyopathy (CM) is the most common cause of end stage heart failure (ESHF). Familial/genetic CMs are underdiagnosed CM subtypes, and recognition of these CMs has implications for the treatment of patients and their relatives. We aimed to characterize the screening for familial/genetic CM in a cohort of patients with ESHF due to nonischemic CM.

Methods:
Single-center, retrospective analysis of patients with nonischemic CM who underwent left ventricular assist device or heart transplantation (LVAD/HT) from 1992-2019. Demographics, clinical characteristics, family history (FHx), and genetic testing results were collected.

Results:
A total of 248 patients (73 women [29%]) were included. Age at CM diagnosis was 23 years (IQR 20.5, 29.5) for patients with suspected or confirmed familial, genetic, or noncompaction CM versus 44 years (IQR 35, 52) for other nonischemic etiologies (p<0.001). A 3-generation FHx was reported for 23% of patients; 25 (18 men [72%]) underwent genetic testing. Median time between LVAD/HT and genetic testing was 519 days. Five patients underwent genetic testing prior to LVAD/HT. Cascade screening was recommended in 15/25 (75%). Twelve of 25 (48%) had a disease-causing genetic variant identified (Table). Among these 12, median age at CM diagnosis was 25.5 years (IQR 20.5, 35) compared with 40.5 years (IQR 27, 45.5) for those (n=13) who underwent genetic testing but did not have any causative variants identified.

Conclusion:
In this cohort of patients with ESHF due to nonischemic CM, only 23% had a documented 3-generation FHx, only 10% underwent genetic testing, most patients underwent genetic testing after LVAD/HT, and patients with suspected or confirmed familial/genetic CM presented at significantly younger ages. Our findings highlight opportunities to improve underdiagnosis of familial/genetic CM, especially for those patients who present with advanced HF in the third decade of life.
Abstract 12340: Vascular Pathology of Critical Limb Ischemia; Comparison of Plaque Characteristics Between Anterior and Posterior Tibial Arteries
Authors: Koyama Yutaka , Hao Hiroyuki , Migita Suguru , Shimodai-Yamada Sayaka , Suzuki Mayumi , Uto Kenta , Okumura Yasuo
Published: June 2023

Background and aims:
The number of patients with peripheral arterial disease (PAD) is increasing, and when it develops into critical limb ischemia (CLI), the 5-year mortality rate is as high as 50%. Nevertheless, there are few histopathological reports of PAD. We analyzed the pathology of anterior tibial artery (ATA) and posterior tibial artery (PTA) obtained from the patients who underwent low extremity amputation due to CLI.

Methods:
Thirty tibial arteries removed from 15 lower limb amputation specimens were examined. Dissected ATAs and PTAs were subjected to ex-vivo soft X-ray radiography, followed by pathological examination using 860 transverse sections.

Results:
The distribution of calcified area per vessel area is significantly higher in PTAs than in ATAs by the soft X-ray radiography images (ATAs, 48.3% ± 19.2 versus PTAs, 61.6% ± 23.9;
p
< 0.05). Morphological and immnunohistological examination revealed eccentric plaque with necrotic core and macrophage infiltration was prominent in ATAs than in PTAs(ATAs, 48.3% ± 19.2 versus PTAs, 61.6% ± 23.9;
p
< 0.05) (ATAs, 48.3% ± 19.2 versus PTAs, 61.6% ± 23.9;
p
< 0.05). Moreover, thromboembolic lesions were frequently identified in PTAs than in ATAs (ATAs, 11.1% versus PTAs 15.8%;
p
< 0.05). The proportion of intimal calcification area and medial calcification area were significantly higher in ATAs and PTAs, respectively (intima; ATAs, 0% [0-16.8] versus PTAs, 0% [0-11.7%];
p
<0.05, media; PTAs, 38.2% versus ATAs, 15.7%;
p
< 0.05).

Conclusions:
Histological features were strikingly different among these arteries of the patients with CLI. To clarify the pathological features of CLI may contribute to establish the therapeutic strategy for PAD, particularly below the knee arteries.
Abstract 12357: Prevalence and Impact of Obesity Status in Current Randomized Controlled Trials of Catheter Ablation for Treatment of Atrial Fibrillation: A Systematic Review
Authors: Aroudaky ahmad , Almerstani Muaaz , Khaing Eh , Haynatzki Gleb , Schleifer John , Payne Jason , Easley Arthur , Khan Faris , Windle John R , Tsai Shane , Anderson Daniel R , Naksuk Niyada
Published: June 2023

Introduction:
The prevalence of obesity among patients with AF and its impact on catheter ablation outcomes remain controversial. We aimed to examine the proportion of obese participants enrolled in current AF ablation RCTs and outcomes of ablation among patients with obesity.

Methods:
We systematically searched PUBMED for RCTs examining catheter ablation for treatment of AF published between 01/2019 to 03/2022. When mean and standard deviation (SD) were available, normal distribution was assumed and a z-score was used to estimate the proportion of obese participants. A trial was classified as group A and B when conducted in countries where obesity is defined as BMI ≥30 and ≥25 kg/m
2
, respectively.

Results:
Of 26 RCTs comprising 1,582 participants, 19 (73.1%) trials reported the BMI of study participants, but only 2 (7.7%) specified the proportion of obesity (15.5% and 39.0%). Two trials excluded participants with BMI>35 kg/m
2
. In group A (N
1
=17), the mean BMI was 28.8±1.4 kg/m
2
with estimated obese participants of 39.7% (IQR 38-45 kg/m
2
). The mean BMI in group B (N
2
=9) was 24.9±1.1 kg/m
2
with estimated obese participants of 47.1% (IQR 37-50 kg/m
2
), Figure. Subgroup analysis examining the effect of catheter ablation according to the BMI status was not reported in any RCTs. Bivariate or multivariate analysis evaluating the effect of BMI or body weight were used in only 4 (15.4%) RCTs. The results suggested that BMI or body weight did not affect their main findings with risk ratio of 0.97-1.00.

Conclusion:
Current AF ablation RCTs underreport the actual proportion of participants with obesity. However, using the available mean BMI of the study subjects, concomitant obesity among AF patients was highly prevalent and identified in 40-50%. The impact of obesity on the main findings is not fully reported; thus, efficacy of AF ablation among obese patients could not be concluded.