bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16655: Impact of Age, Race, and Arterial Stiffness on Ambulatory Heart Rate-Stroke Volume Counter-Regulation
Authors: Elsayed Sherif M , Elango Kalaimani , Ahmed Rahil , Bhura Sajeer , Osmond Peter J , Izzo Joseph L
Published: April 2024

Background:
We have previously reported a strong negative correlation between stroke volume index (SVI) and heart rate (HR) within and between normal and hypertensive individuals and have defined the slope of the SVI-HR relationship as an index of the efficiency of rate-volume counter-regulation. SVI-HR slope may also reflect the efficiency of diastolic filling (Starling forces).

Objective:
To investigate whether SVI-HR slope is influenced by demographic or hemodynamic variables.

Design and method:
24 hr. ambulatory pulse wave analysis (PWA, Mobil-O-Graph, IEM, Stolberg, DE) with a 20-minute sampling interval was performed in a convenience sample of 94 normal and hypertensive subjects. Systolic (S) and diastolic (D) blood pressure (BP), pulse pressure (PP), HR, cardiac index (CI), SVI (= CI/HR) and the slope of the SVI-HR regression line were calculated in each subject. Group data were analyzed using IBM SPSS software with Pearson linear regression and stepwise multiple linear regression methods.

Results:
Characteristics of the cohort were (mean ± SD): age 57±17 years, weight 82.5±19 kg, 59% women, 62% Caucasians, BP 135±20/80±14 mm Hg, and HR 69±12 beats/min). There was a strong negative correlation between individual SVI and HR values (r = -0.53; p < 0.001). Slope correlated with age (r=0.268), race (greater in Blacks), and PP (r=0.222) (all p<0.05). Stepwise multiple linear regression modeling yielded the following relationship: SVI-HR Slope = - 0.31 race + 0.227 PP - 0.535 (multiple r = 0.381, p<0.001); excluded variables were: age, gender, height, weight, 24 hr. SBP, MAP and DBP.

Conclusions:
There is a strong negative correlation between HR and SVI; the slope of this relationship is affected by age and PP (lower slope in older people or with wide PP) and race (greater slope in Blacks). In a multiple regression model, age was replaced by PP but age and PP are closely related to arterial stiffness. Lower SVI/HR slope with age may signify a parallel increase in “cardiac stiffness” or diastolic dysfunction. Why blacks exhibit more effective rate-volume counter-regulation is unknown.
Abstract 16659: Nogo-B Receptor is Required for the Recruitment of Vascular Smooth Muscle Cells to Developing Blood Vessels
Authors: Rana Ujala , Hu Wenquan , Fang Zhi , Liu Zhong , Zhao Baofeng , Miao Qing R
Published: April 2024

The blood vessel maturation involves the coordination of two cell types - endothelial cells (EC) and vascular smooth muscle cells (VSMC). Hence, understanding of EC and VSMC migration is an essential step in developing new therapeutic approaches for diseases-associated with blood vessel maturation defects. PDGF plays a critical role in blood vessel maturation by promoting VSMC proliferation and migration via Ras signaling pathway. Although Nogo-B receptor (NgBR) was identified as a cell surface receptor special for the ligand Nogo-B, it acts as a scaffold protein requested for Ras translocation to the plasma membrane, which is a critical step for Ras activation by PDGF receptor and other receptor tyrosine kinases. NgBR is expressed in both EC and VSMC. Previous reports demonstrated the genetic deletion of NgBR in endothelial cells causes the embryonic lethality due to cerebrovascular defects in mice. Here, we further elucidate the roles of NgBR in regulating the recruitment of VSMC in the developing blood vessels. The genetic deletion of NgBR in VSMC also results in embryonic lethality due to impaired VSMC coverage on blood vessels and hemorrhage. Mechanistically, our data demonstrated that NgBR is required for PDGF-induced Ras signaling pathway and VSMC migration. Interestingly, we also appreciate the defects of VSMC recruitment in the blood vessels of NgBR EC-specific knockout mice. Gene profile analysis reveals that NgBR knockdown decreased the expression of PDGF in EC. Collectively, these data demonstrate that NgBR is an integral part of blood vessel maturation process by facilitating VSMC recruitment. Our results suggest that NgBR may be one of the essential genes coordinating the blood vessel development.
Abstract 16665: Tead1 - a Novel Cell-Autonomous Regulator of Mitochondrial Function in Cardiomyocytes
Authors: Liu Ruya , Jagannathan Rajaganapathi , Li Feng , Lee Jeongkyung , Yechoor Vijay K , Moulik Mousumi
Published: April 2024

Introduction:
Mitochondrial (mito) dysfunction occurs in most forms of heart failure (HF). We previously demonstrated that TEAD1, the transcriptional effector of Hippo pathway, plays a critical non-redundant role in adult CM homeostasis and its loss-of-function (LOF) leads to rapid-onset HF and dilated cardiomyopathy (DCM). Objective of this study was to determine requirement of TEAD1 in regulation of mito function in CMs.

Hypothesis:
TEAD1 is required for normal CM mito function and a loss of this regulation contributes to the rapid-onset lethal DCM with
Tead1
deletion.

Methods and Results:
Conditional
Tead1
deletion in adult CMs (
Tead1
-icKO) was achieved after 3 wks of tamoxifen (TM) diet in 6 wks old mutant mice (floxed

Tead1, Tead1
F/F

mice crossed with
Myh6-CreER
mice
)
. Within 3 wks of
Tead1
deletion,
Tead1
-icKO mice developed acute lethal DCM with LV dilation and severe systolic dysfunction. Gene-set enrichment analysis from the
Tead1
-icKO myocardial transcriptome, followed by qPCR validation, revealed mito-related genes as the top regulated gene sets. ChIP-seq, using TEAD1 antibody, in adult mouse hearts revealed that TEAD1 occupies the promoter/enhancers of multiple genes regulating mito biogenesis and function. To investigate if TEAD1 regulates OXPHOS, mito oxygen consumption rates (OCR) from mitochondria isolated from control and
Tead1
-icKO mouse hearts were analyzed by Oroboros respirometry.
Tead1
-icKO heart mitochondria had significantly decreased OCR with both palmitoylcarnitine and pyruvate/malate substrates. Primary neonatal CMs with
ex vivo
TEAD1 LOF (adenoviral-Cre transduction of

Tead1
F/F

neonatal CMs) showed diminished maximal OCR (Seahorse XF24 analyzer), demonstrating that TEAD1 regulation of OXPHOS in CMs is cell autonomous. (Refer to Fig)

Conclusions:
Taken together, our data demonstrate that TEAD1 is a direct transcriptional regulator of a large network of mitochondrial function and biogenesis related genes, is a novel cell-autonomous regulator of CM mitochondrial function and is critical for maintenance of adult CM homeostasis.
Abstract 16673: Exposure to Ambient Polycyclic Aromatic Hydrocarbons Results in Lipoxygenase Activation and Decreased Paraoxonase-1 Activity
Authors: Lin Yan , Yin Fen , Qiu Xinghua , Ramanathan Gajalakshmi , Rea Nolan D , Faull Kym F , Zhu Yifang , Araujo Jesus A
Published: April 2024

Introduction:
There is cumulative evidence in support of causal associations between exposure to air pollution, atherosclerosis and cardiovascular mortality. However, the mechanisms for responsible for those associations are not known. Animal studies have found that exposure to ambient particulate matter (PM) promotes lipoprotein oxidation, together with decreased paraoxonase 1 (PON-1) activity, and activation of 5- and 12/15-lipoxygenase pathways but evidence on human subjects is lacking.

Hypothesis:
Exposure to polycyclic aromatic hydrocarbon (PAHs), a group of airborne chemicals originated from combustion sources highly prevalent in ambient PM, inhibit PON-1 activity and induce oxidative stress.

Methods:
We recruited 26 healthy non-smoking young adults traveling from Los Angeles to Beijing in summer. Paired urine and plasma samples were collected before (LA
1
), during (BJ) and after (LA
2
) the travel. Urinary monohydroxylated metabolites of five PAHs (i.e. naphthalene, dibenzofuran, fluorene, phenanthrene and pyrene) were measured as indicators of PAHs exposure. We also assessed plasma levels of PON-1 enzymatic activities, 5-, 12- and 15- hydroxyeicosatetraenoic (HETE) acids as well as 9- and 13-hydroxyoctadecadienoic acid (HODE) acids, which are oxidative products of polyunsaturated arachidonic and linoleic acid. Data was analyzed by a mixed-effect model with random intercepts.

Results:
Four out of five PAHs metabolites (all except for naphthalene) were elevated by 1.6-9.0 folds (
p
<0.001) in BJ as compared with levels in LA
1
or LA
2
indicating increased exposure to PAHs in BJ. On the contrary, there was a significant decrease in plasma paraoxonase and arylesterase activities (
p<
0.05) without changes in plasma PON-1 concentration, indicating functional alteration of PON-1. There was also a significant increase in plasma levels of all HETEs and HODEs (
p<
0.05) indicating elevated oxidative stress. The increase in 5-, 12- and 15-HETEs observed in BJ remained statistically significant after normalization by arachidonic acid (
p<
0.05), indicating activation of 5 and 12/15 lipoxygenases. In addition, there were strong associations (
p
<0.05) between changes in all PAHs (except naphthalene), with HETEs, HODEs and changes in PON-1-associated paraoxonase and arylesterase enzymatic activities, after adjusting city’s effects.

Conclusion:
PM promotes atherosclerosis likely by its high content in PAHs, and their concomitant pro-oxidative effects resulting in activation of lipoxygenases and inhibition of PON-1 activity.
Abstract 16681: Early Left Ventricular Dysfunction in Healthy Young Adults Born Premature
Authors: Goss Kara N , Beshish Arij G , Macdonald Jacob , Barton Gregory P , Chesler Naomi C , Francois Christopher J , Wieben Oliver , Eldridge Marlowe W
Published: April 2024

Rationale:
Preterm birth, or less than 37 weeks completed gestation, affects one in 10 live births in the United States. Moderate to extreme premature birth, or less than 32 weeks gestation, is associated with up to a 17-fold increased risk for the development of heart failure in adolescents and young adults. Here, we sought to characterize left ventricular (LV) function in young adults born premature.

Methods:
Adults born preterm (n=11; gestational age 28.2±0.8 weeks; current age 27±1 years) were recruited from the Newborn Lung Project at the University of Wisconsin-Madison, a prospective cohort of infants born 1988-1991 with birth weight <1500 g. Controls were recruited from the general population (n=12; age 26±1 years). All subjects were free from adult cardiopulmonary disease. Subjects underwent cardiac magnetic resonance imaging (MRI) on a 3.0T scanner. Measures included standard assessment of LV function and LV strain. 4D flow imaging was acquired with a radially-undersampled PC VIPR sequence to assess systolic and diastolic LV kinetic energy, and corresponding LV energetic efficiency was defined as stroke volume normalized by the systolic and diastolic kinetic energy . Mann-Whitney tests were performed to assess for statistical significance (p<0.05).

Results:
Young adults born premature had significantly smaller chamber volumes, even when indexed to body size (table 1). However, stroke volume was maintained due to a higher ejection fraction. Cardiac output and index were significantly higher in young adults born premature, due to a higher resting heart rate. Strain analysis confirmed a hyperdynamic LV. 4D flow demonstrated a significantly higher LV energy cost, resulting in an energetically inefficient LV.

Conclusions:
Otherwise healthy young adults born premature demonstrate a hypercontractile, energetically inefficient LV, which may provide mechanistic insight into the increased risk for heart failure in this high-risk population.
Abstract 16688: CZT Equilibrium Radionuclide Angiography (ERNA) Detects Improvements in Right Ventricle Size and Function for Pulmonary Arterial Hypertension Participants Intensifying Therapy
Authors: Light Allison , Lachant Daniel , Mackin Maria , Schwartz Ronald , White R. James
Published: April 2024

Introduction:
Pulmonary Arterial Hypertension (PAH) is associated with pruning and vasconstriction of the pulmonary arteries, resulting in right ventricular (RV) failure and death. RV size and function are among the most powerful prognostic predictors for disease outcomes and can change in response to therapy. However, obtaining quantitative RV information remains challenging with echocardiography, while cardiac MRI remains expensive, claustrophobic, and relatively less accessible.

Hypothesis:
CZT ERNA is a simple and readily available cardiac imaging technique that will measure changes in RV size and function for PAH participants intensifying therapy (RVEF, RVEDV, RVESV).

Methods:
D-SPECT (Spectrum Dynamics) CZT-ERNA was performed on 24 participants using low dose (approximately 10 mCi Tc-99m TCO4
-
; ~2.5 mSv), 10 minute imaging protocol: 12 were imaged just prior to starting or intensifying therapy and again 6 months later (Active), and 12 age- and sex-matched controls on stable therapy were imaged twice within a 3 week period. Additionally, 6 minute walk distance, laboratories (including NTproBNP) and WHO functional class were assessed at the time of each scan. All scans were processed using Cedars Sinai QBS automatic software; we did manual re-processing when chamber separation was poor or extra-cardiac activity was substantial (n=22/40 scans).

Results:
All 24 participants completed two scans; four (2 Active, 2 control) were excluded from paired analysis due to low intensity images on one scan (of a pair), and one Active participant was excluded due to clinical worsening requiring hospitalization. There were no adverse events related to imaging. RVEF (45% ± 3.5 vs 55% ± 4.2; p=0.008) and RV stroke volume (89mL ± 10.3 vs 108mL ± 12.3; p=0.03) improved in the active group but were stable in the control group (RVEF= 58% ± 3.7 vs 56% ± 5.0; RVSV=108mL ± 12.9 vs 116mL ± 16.6). A participant with particularly striking improvement is illustrated below. Scan times were 10 minutes with total testing time between 60-90 min.

Conclusions:
CZT-ERNA is quick, easy and seems effective for obtaining quantitative measures of the RV in PAH.
Abstract 16693: Standalone Quantitative
18
F-NaF Coronary PET Fused With Prior Deep-Inspiration Coronary CT Angiography for Improved Patient Workflow
Authors: Kwiecinski Jacek , Lee Sang-Eun , Dey Damini , Cadet Sebastien , Lassen Martin L , Jansen Maurits , Dweck Marc R , Newby David E , Chang Hyuk-Jae , Yun Mijin , Berman Daniel S , Slomka Piotr J
Published: April 2024

Introduction:
18
F-NaF PET holds promise in distinguishing high-risk plaques in patients with coronary artery disease. The current imaging protocol requires a hybrid single-session acquisition of coronary computed tomography angiography (CTA) and PET. This approach does not allow high-risk patient selection for
18
F-NaF imaging based on prior CTA findings. We aimed to determine whether prior deep inspiration CTA fused with a subsequent PET-only scan allows reliable evaluation of coronary
18
F-NaF uptake.

Methods:
Twenty-five patients (age 65±6 years, 68% males) underwent clinical CTA (CTA1) on a dual-source CT scanner and subsequently combined
18
F-NaF PET/CTA (CTA2) imaging on a hybrid PET/CT scanner within 16 [9,28] days. We fused CTA1 with
18
F-NaF PET (PET) and compared the visual pattern of activity, maximal standard uptake values (SUVmax) and target to background ratio (TBR) measurements on prior-CTA (PET/CTA1) versus hybrid (PET/CTA2) cardiac motion corrected PET images.

Results:
On PET/CTA2, 118 coronary plaques were identified. Thirty-six coronary segments from 14 (56%) patients had high
18
F-NaF uptake (TBR>1.25), while 82 segments had lesions with
18
F-NaF TBR ≤1.25. Uptake in all lesions was categorized identically on co-registered PET/CTA1. There was no difference in
18
F-NaF uptake between PET/CTA1 and PET/CTA2 (SUVmax: 1.46±0.59 vs. 1.45±0.57, p=0.53; TBR:1.28±0.55 vs. 1.26±0.53, p=0.41). Repeatability of uptake measurements was excellent with intraclass correlation coefficients of 0.98 (95% CI 0.97 to 0.99, p<0.001) and 0.94 (95% CI 0.92 to 0.96, p<0.001) and limits of agreement of ±0.18 and ±0.19 for SUVmax and TBR respectively.

Conclusions:
Coronary CTA/PET protocol with CTA first followed by PET-only allows for reliable and reproducible quantification of
18
F-NaF coronary uptake. This approach may facilitate selection of high-risk patients for PET-only imaging based on results from prior CTA, providing a practical workflow for clinical application.
Abstract 16698: Variation in Systolic Blood Pressure Among Low-Socioeconomic Urban Dwellers is Associated With Travel Distance by Mode of Transportation
Authors: Chua Rhys , Kolak Marynia , Besser Stephanie A , Tung Elizabeth L , Anyanwu Emeka , Liao James K , Tabit Corey E
Published: April 2024

Introduction:
Hypertension affects one third of American adults and is especially common among low-socioeconomic urban dwellers. Studies suggest that poor access to a pharmacy is associated with elevated blood pressure (BP). Residents on the South Side of Chicago typically travel locally using three common modes of transportation - walking, riding the city bus, or driving - based on the distance of the trip. Based on previous literature, walking is preferred for distances less than 3 km, taking the city bus is preferred for distances 3-10 km, and driving is preferred if possible for distances greater than 10 km. Because distances from home to the pharmacy at thresholds between each mode of transportation (i.e. a long walk vs. a short bus ride) could cause logistical uncertainty for patients, we hypothesized that blood pressure is higher for patients living at threshold distances from the pharmacy they typically use.

Methods:
Medical records of adult South Side residents who received care at the University of Chicago’s outpatient clinics from 2012 through 2017 were reviewed. Blood pressure (BP) measurements for each patient were averaged and each patient’s home and pharmacy addresses were geocoded. We calculated the walking and driving distance from each patient’s home to his or her pharmacy. The relationship between BP and travel distance was compared using Spearman rank correlation and Fisher’s exact test.

Results:
47,084 patients were included in the study. Mean systolic BP was significantly lower for patients living ≤1 km from their pharmacy than for patients living farther (p<0.0001). Mean systolic BP was highest at common distance thresholds for changing mode of transportation among urban dwellers (2-3 km and 10-20 km, Figure). Diastolic BP was not associated with distance from home to pharmacy.

Conclusions:
Among South Side Chicagoans, systolic BP is lowest for patients living ≤1 km from their pharmacy and highest at distance thresholds for walking, riding the city bus, or driving. Interventions to improve BP control among urban dwellers may benefit from targeting patients who live at threshold distances from their pharmacy.
Abstract 16699: Single Cell Sequencing Reveals Changes in Monocytes in Patients With Mutations Leading to Clonal Hematopoiesis: Implications for Prognosis of Ischemic Heart Disease
Authors: Abplanalp Wesley T , John David , Assmus Birgit , Dorsheimer Lena , Rasper Tina , Ortmann Christina , Ecke Andreas , Abou-El-Ardat Khalil , Schmid Tobias , Brüne Bernhard , Wagner Sebastian , Serve Hubert , Hoffmann Jedrzej , Seeger Florian , Rieger Michael A , Zeiher Andreas M , Dimmeler Stefanie
Published: April 2024

Background:
Cardiovascular disease is the leading cause of death worldwide; the majority of these deaths are due to ischemic heart disease (IHD). Recent data suggest that inflammation causally contributes to IHD. However, the detailed characterization of the individual inflammatory status of individual cells on a cellular level is missing. Single cell sequencing provides a novel opportunity to define subsets of hematopoietic cells mediating inflammation in humans. Therefore, we determined the inflammatory burden driven by heterogeneity in monocytes in subjects with IHD.

Results:
We sorted circulating CD31+ cells of patients with IHD versus healthy controls (n=4 per group) and performed single-cell RNA-sequencing. Unsupervised clustering of the entire 37679 cells generated 19 clusters with unique transcriptional profiles. Cells of patients with IHD showed a strikingly different pattern and dysregulated pathways compared to healthy controls. Among the specific dysregulated genes were S100A8, interleukin 1b, thrombospondin-1 and matrix metalloprotease-1, which were confirmed by FACS and qRT-PCR in a validation cohort. Because of the profound differences in each of the individual patients, we evaluated the occurrence of somatic mutations leading to clonal hematopoiesis (CHIP), which recently was shown to be increased in patients with atherosclerosis. Indeed, two of the four patients revealed a mutation in the DNA methyltransferase DNMT3A. DNMT3A mutations were associated with a change in known DNMT3A target genes such as the pro-inflammatory genes CXCL1, CXCL2 and IL6. To determine the impact of DNMT3A mutations on prognosis, we sequenced a cohort of n=200 patients with IHD. Among these patients n=13 harbored a DNMT3A mutation. Mortality of non-CHIP carriers was 23%, but 62% for DNMT3A mutation CHIP-harboring patients (p=0.012).

Conclusions:
This study shows that circulating cells derived from CHIP-harboring individuals have unique phenotypes. DNMT3A mutations strongly predict increased mortality in patients with ischemic heart failure relative to subjects without CHIP mutations.
Abstract 16702: Does Perceval Sutureless Aortic Valve Offer Advantages Over Traditional Surgical Aortic Valve Replacement?
Authors: Robich Michael P , Gelb Daniel J , Quinn Reed D , Robaczewski David , Radziszewski Dorothy , Malenka David J , Ross Cathy S , Iribarne Alexander , DiScipio Anthony W , Kramer Robert S
Published: April 2024

Introduction:
The Perceval S is a sutureless (SLV), rapid deployment, bovine pericardial aortic prosthesis on a nitinol stent. The role of this valve in the age of standard surgical and transcatheter aortic valve replacement is being defined. There are no data on cost from the United States.

Methods:
We performed a retrospective review of aortic valve replacement, comparing SLV with traditional sutured AVR (SAVR) at a single center between August 2015 and December 2017. Three surgeons who use both valve types performed 143 SLV and 117 SAVR procedures. Exclusions included mechanical valves, homografts, endocarditis, aortic dissection or emergency status. Hospital cost data (including valve cost) were reviewed. Inverse probability weighting (IPW) was used to balance the groups.

Results:
Compared to SAVR, SLV patients were significantly older (Table). Additional procedures (i.e., CABG) were performed with equal frequency. Minimally invasive access was more common for SLV. Cross clamp times were significantly shorter for SLV than SAVR, but were comparable when other procedures were performed. After IPW, groups were well balanced. SLV patients had higher rates of permanent pacemaker placement, pleural effusions and a greater post-procedure drop in platelet counts. There were no differences in rates of postoperative transfusions, atrial fibrillation, stroke, renal failure, prolonged ventilation, length of stay or in-hospital mortality. Hospital costs were comparable. Pacemaker rates for SLV decreased over time (25% in 2015 to 4% in 2017,
Ptrend
=.003).

Conclusion:
SLVs were selectively used in an older population and were associated with shorter cross clamps times. They were not associated with an increased risk of adverse events other than pacemaker placement, for which there was a learning curve and despite this, their associated cost of care was not significantly great than for SAVR. This valve may be advantageous in older, higher risk patients requiring concomitant operations.
Abstract 16710: Racial Disparities in Outcomes in Women Undergoing Percutaneous Intervention
Authors: Iantorno Micaela , Torguson Rebecca , Gajanana Deepakraj , Kolm Paul , Rogers Toby , ben-dor Itsik , Suddath William O , Satler Lowell , Garcia-garcia Hector , weintraub William S , Waksman Ron
Published: April 2024

Introduction:
Cardiovascular disease is the leading cause of death in men and women, blacks and whites. Women are underrepresented in clinical studies. African-American women have a higher coronary heart disease mortality risk than their white counterparts. However, there exists limited outcomes data for black women (BW) compared to white women (WW) after percutaneous coronary intervention (PCI).

Hypothesis:
The aim of this retrospective analysis was to evaluate the 1 year major cardiovascular events (MACE) in patients undergoing PCI based on gender and race

Methods:
Within our PCI database we identified 4776 patients who underwent PCI from 2003 to 2016. Of those 1,916 were BW and 2,860 were WW. MACE/target vessel revascularization (TVR) at 30 days and 1 year were assessed and proportional Cox hazard model analyses was performed to assess outcomes after adjustment for confounding factors (i.e. age, BMI, presentation with acute M, diabetes, smoking, history of CAD, family history of CAD, hyperlipidemia, hypertension, prior coronary intervention, chronic kidney disease (CKD)).

Results:
Characteristics of the patient population is shown in the table. BW presented at younger age and had significantly higher rate of risk factors. BW were significantly sicker than WW. Periprocedural and in-hospital were similar between the 2 groups except for vascular complications more likely in WW (4.3% vs 2.6%; p=0.003). At 30 days and 1 year, the rate of MI, TVR and stent thrombosis (ST) was significantly higher in BW (Figure). There was a large difference in median income, $102,250 for WW vs. $80,150 for BW, but it had no effect on the outcome (HR = 1.00, p = 0.362). After adjusting for confounding factors BW were 1.6 times more likely to experience MI at 1 year than WW (HR 1.6, 05%CI 1.04-2.49, p= 0.03).

Conclusions:
In this large cohort of women with coronary artery disease undergoing PCI we observed significant race disparities in MI rate at 1 year even after adjustment for clinical presentation and cardiovascular risk factors
Abstract 16712: Cardiovascular Event Rates Among Patients With Peripheral Arterial Disease in a United States Administrative Insurance Claims Database
Authors: Mues Katherine E , Philip Kiran , Bradbury Brian D , Schneeweiss Sebastian S , Monda Keri L
Published: April 2024

Introduction:
A sub-analysis of the cardiovascular (CV) outcomes trial, FOURIER, showed that among patients with peripheral arterial disease (PAD), the PCSK9 inhibitor evolocumab reduced the risk of myocardial infarction (MI), stroke, and cardiovascular death by 27% over 2.2 years compared to those on moderate- or high-intensity statins. To contextualize the impact of these findings, we estimated rates of CV events and treatment utilization among a population with PAD in the real world.

Methods:
We identified patients with a first diagnosis of PAD between January 1, 2008 and October 1, 2016 in the Truven MarketScan claims database. Patient were required to have continuous enrollment 365 days prior to and 1 day following the index date. Medication use was evaluated in the one year prior; comorbidities were evaluated using all available data prior to index. Patients were followed until the occurrence of a CV hospitalization, disenrollment, death, or October 1, 2016. Event rates and corresponding 95% confidence intervals were calculated. Analyses were conducted in the Aetion platform.

Results:
We identified 565,942 subjects with PAD; mean age was 71 years, 49% were female, 67% had Medicare supplemental insurance, 37% had Type 2 diabetes (T2DM), 13% a prior MI or ischemic stroke (IS), and 10% critical limb ischemia (CLI). During baseline, 45% of patients filled an anti-hypertensive, 43% a statin, 18% an anti-platelet, and 11% an anti-coagulant. Patients were followed for a median of 1.4 years. Incident event rates were 42.7, 24.6, 12.9, 8.9, and 1.1 per 1000 person-years (py) for the composite, MI, coronary revascularization (CABG/PCI), IS, and unstable angina (UA) respectively. Rates were higher among those with history of MI or IS, T2DM, and CLI (Table).

Conclusions:
These findings suggest that among a real world population of PAD patients there is underutilization of effective therapies prior to diagnosis and substantial burden in terms of cardiovascular residual risk.
Abstract 16721: Cardiovascular and Metabolic Risk Profile of Nonalcoholic Fatty Liver Disease Patients and Liver Transplant Recipients
Authors: An Kyungeh , Salyer Jeanne , Siddiqui Shadab
Published: April 2024

Introduction:
Cardiovascular disease (CVD) mortality is a growing concern in chronic liver disease (CLD) patients. Although prevention of CVD should target the whole spectrum of CLD, earlier CLD such as nonalcoholic fatty liver disease (NAFLD) vs. advanced CLD such as liver transplant recipients (LTR) may have different risk profiles. Yet, the differences in CVD and metabolic risk profiles between NAFLD and LTR patients have not been investigated.

Hypothesis:
We hypothesize that, between NAFLD and LTR patients, there are differences in (1) global CVD risk measured by Framingham Risk Score (FRS), (2) systemic inflammatory biomarker of hsCRP, and (3) metabolic risk factors, such as blood pressure (BP), glucose, lipid profile, and anthropometric indices including body mass index (BMI) and waist circumference.

Methods:
27 adult LTR who exhibited no history or current CVD or rejection of transplantation were compared to 23 biopsy-confirmed NAFLD patients. Global CVD risk was calculated using the FRS equation. Plasma level of hsCRP, fasting glucose, lipid profile including total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), and triglycerides(TG) were analyzed using ELISA. Anthropometric analysis was conducted to assess obesity.

Results:
LTR compared to NAFLD patients had (1) lower FRS (7.15±6.15 vs. 15.88±11.39%, p<0.001), (2) higher level of hsCRP (36.85±40.60 vs. 4.38±4.73 mg/L, p<0.001), (3) higher systolic BP (132.48±15.18 vs. 123.30±11.24mmHg, p<0.05) and diastolic BP (80.41±9.30 vs. 72.52±6.90 mmHg, p<0.01), higher HDL in both men (46.20±14.72 vs. 38.50±3.62 mg/dl, p=0.044) and women (61.57±11.20 vs. 49.76±11.63mg/dl, p=.042). There were no differences between groups in metabolic dysfunction indices such as fasting glucose, TC, LDL, or waist circumference.

Conclusion:
The liver transplantation does not increase the global CVD risk or the metabolic risks. However, systemic inflammation and suboptimal BP indicate LTR at risk of CVD. Reducing obesity is critical target to both LTR and NAFLD patients. Maintaining BP at optimal level should be the target in LTR whereas improving lipid profile is critical in NAFLD to prevent CVD. Large scale study will inform clinicians with the specific targets of CVD prevention for patients in diverse phases on CLD spectrum.
Abstract 16726: N-Cadherin Overexpression Improves the Reparative Potency of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Infarcted Mouse Hearts
Authors: Lou Xi , Zhao Meng , Fan Chengming , Fast Vladimir , Gao Ling , Tang Yawen , Zhu Wuqiang , Zhang Jianyi
Published: April 2024

Background:
Stem-cell-based therapy is a promising approach for the treatment of myocardial infarction (MI); however, the effectiveness of the treatment is believed to be limited by the poor survival and functional integration of transplanted cells. Within the heart, the adhesion between cardiomyocytes (CMs) is mediated by N-cadherin (CDH2), and CDH2 expression is well correlated with the efficacy of mesenchymal stem cells for myocardial repair. Thus, we determined whether the electrical connectivity, engraftment, and reparative potency of human induced-pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) can be improved via CDH2 overexpression.

Materials and methods:
Conduction velocities were measured in cultured CDH2-overexpressing hiPSC-CMs (CDH2-CMs) and wild-type hiPSC-CMs (WT-CMs) via optical mapping. MI was induced in SCID mice via coronary artery ligation; then, the mice were treated with CDH2-CMs or WT-CMs (310
5
cells/mouse) (i.e., the MI+WT-CM and MI+WT-CM groups, respectively), or with neither experimental treatment (the MI group). The cells were injected directly into the infarcted region of the heart, cardiac function and infarct size were evaluated via post mortem examination, and the engraftment rate was evaluated histologically.

Results:
In-vitro conduction velocities were significantly greater (p<0.05) in CDH2-overexpressing hiPSC-CMs than in wild-type hiPSC-CMs, while in-vivo measurements of cardiac function (left-ventricular ejection fraction and fractional shortening), infarct size, and the hiPSC-CM engraftment/survival rate at week 4 after MI were significantly better in the MI+CDH2-CM group than in MI+WT-CM animals and in both cell-treatment groups than in MI animals .

Conclusion:
N-cadherin overexpression improves the electrical connectivity of cultured hiPSC-CMs, as well as the engraftment/survival and reparative potency of transplanted hiPSC-CMs in infarcted mouse hearts.

Key words:
N-cadherin, Myocardial Infarction, human induced pluripotent stem cells.
Abstract 16746: Single High-Sensitivity Cardiac Troponin I Measurement Using the Siemens Atellica IM Assay to Rule-Out Acute Myocardial Infarction at Presentation in Low Risk in Patients Evaluated in the Emergency Department
Authors: Schulz Karen , Nowak Richard , Christenson Robert , DeFilippi Christopher , McCord James , Sexter Anne , Apple Fred S
Published: April 2024

Introduction:
High sensitivity cardiac troponin (hs-cTn) assays are able to quantitate low concentrations of cTn and provide an opportunity to rule out acute myocardial infarction (MI) at an early stage following a patient’s presentation to an emergency department.

Hypothesis:
The objectives of the current study were to examine the performance of single hs-cTnI measurement strategy to rule out acute MI and predict 30-day safety outcomes at presentation in these patients.

Methods:
This was a prospective, observational study of patients (n = 2342) presenting to US emergency departments with suspected acute coronary syndrome in whom cTnI measurements were obtained using the Siemens Atellica IM High Sensitivity Troponin I Assay (Siemens Healthcare Diagnostics). Clinical data and hs-cTnI results were analyzed to determine: 1) clinical sensitivity and negative predictive value (NPV) for ruling out acute MI and 2) safety outcomes of acute MI and death at 30 days, using the hs-cTnI limit of detection (LoD) 1.6 ng/L concentration.

Results:
Acute MI occurred in 306 patients (13.1%). In patients with a hs-cTnI <LoD (n=421, 18.0%), the clinical sensitivity and negative predictive value (NPV) for acute MI were 100% (95% CI 99.0,100) and 100% (CI 99.3,100), respectively. Further, the sensitivity and NPV for the safety outcome of acute MI or death within 30 days for hs-cTnI <LoD were 99.4% (CI 98.5, 99.9) and 99.5% (CI 98.9, 99.9), respectively. Only 2 patients (0.85%) had an event.

Conclusion:
A strategy of using a single hs-cTnI <LoD at presentation allowed the immediate identification of 18.0% of patients highly unlikely to have acute MI and who were at very low risk for events at 30 days. Additional studies to understand the clinical utility and cost-savings of this strategy are needed.
Abstract 16750: Angiogenesis/Arteriogenesis, the Mechanism for Cardioprotection, in Secreted Frizzled Related Protein 2 Transgenic Mice
Authors: Oydanich Marko , Zhang Jie , Yoon Seonghun , Vatner Dorothey E , Vatner Stephen F
Published: April 2024

Secreted frizzled related protein 2 (sFRP2) has been shown to protect against myocardial ischemia primarily mediated by reducing fibrosis. Our hypothesis is that sFRP2 myocardial ischemic protection induced by permanent coronary artery occlusion (CAO) must involve a primary angiogenesis/arteriogenesis mechanism in order to protect the heart in the chronic absence of blood flow. To test this hypothesis, we induced permanent CAO for 1 week in cardiac specific sFRP2 transgenic (TG) mice (n=12), which exhibited reduced infarct size vs. their wild type littermates (WTL; n=13) (16±1 vs. 25±2%) and improved left ventricular ejection fraction (LVEF) (61±6 vs. 45±6%). These salutary effects were accompanied by angiogenesis (170% increase in capillary proliferation and a 54% increase in capillary density) and arteriogenesis (106% increase in arteriole proliferation). sFRP2 increased
in vitro
tubule formation in HUVEC cells by 46% (p<0.05), compared to vehicle. As expected, sFRP2 TG mice also exhibited decreased remote fibrosis, compared to WTL (1.6±0.1 vs.± 3.7±0.3%; n=4-6/group). ATF6, an ER stress response transcription factor, was upregulated in sFRP2 TG mice. When ATF6 was blocked with AEBSF, sFRP2 TG mice no longer demonstrated cardioprotection with permanent CAO, as reflected by similar infarct size, LV EF, capillary and arteriolar proliferation observed in WTL. cTGF, a pro-angiogenic factor, was also upregulated in sFRP2 TG mice. Blocking cTGF with a cTGF antibody, eliminated the increased tubule formation with sFRP2 treatment. AEBSF also eliminated the increased cTGF in sFRP2 TG, confirming ATF6 as the upstream regulator of cTGF, responsible for the angiogenesis and arteriogenesis observed in the sFRP2 TG mice. To determine if angiogenesis/arteriogenesis was the initiating mechanism inducing cardioprotection, blood flow, measured ultrasonically at 1 day following CAO, was increased significantly more, p<0.05, in the ischemic zone of sFRP2 TG mice (2.1±0.46 A.U.) compared with blood flow in WTL (0.4 ±0.09 A.U.). Thus, angiogenesis/arteriogenesis appears to be the primary cardioprotective mechanism induced by sFRP2, with reduced fibrosis playing a secondary role.
Abstract 16773: Ablation of Cardiac Myosin Binding Protein-C in Human iPSC- Engineered Cardiac Tissue Model Causes Increased Calcium Sensitivity and Accelerated Contractile Kinetics
Authors: Ralphe John C , de Lange Willem J , Hernandez Jonathan J , Jacobs Derek R , Kreitzer Caroline R
Published: April 2024

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disease that can cause sudden cardiac arrest, diastolic dysfunction and heart failure. Mutations in cardiac myosin binding protein-C (cMyBP-C), a regulator of contractility, are among the most prevalent causes of HCM. cMyBP-C truncation mutations may affect as many as 1 in 1,600 Americans. Though murine models of cMyBP-C ablation have aided in understanding the role of cMyBP-C in health and disease, they are limited by differences in cardiac physiology between mice and humans. iPSC technology now allows researchers to study the effect of HCM mutations in iPSC-derived cardiomyocytes from HCM patients and controls, however differences in genetic background between patients and controls and clonal variation remain confounders.

We hypothesized that cMyBP-C ablation in human cardiomyocytes would primarily alter cardiac contractility.

CRISPR/Cas9 was used to introduce frame shift mutations in cMyBP-C in the well characterized DF19-9-11T human iPSC line. Human iPSCs were differentiated into cardiomyocytes and then cast into an integrated 3D engineered cardiac tissue (ECT) model for functional testing against non-targeted isogenic controls.

Homozygous cMyBP-C ablation significantly accelerated contraction (CT
100
= 219±3 vs. 235±5ms; p = 0.02) and early relaxation (RT
50
= 144±2 vs. 167±4ms; p <0.001), while late relaxation was slowed (RT
50-90
= 127±2 vs. 112±2ms; p <0.001; n=6 for each group). These accelerated contractile kinetics were accompanied by a significantly blunted response to adrenergic stimulation and an increase in Ca
2+
sensitivity. Heterozygous cMyBP-C ablation resulted in acceleration in relaxation kinetics (RT
50
= 148±7 vs. 167±4ms; p = 0.04 and RT
50-90
= 96±4 vs. 112±2ms; p = 0.002), without significantly affecting the rate of contraction.

The accelerated kinetics of contraction and early relaxation in cMyBP-C null ECT provides important human evidence that cMyBP-C acts as a brake on cardiac contractility. These data provide strong evidence that the human model system can be used to study the function of cMyBP-C and provide a platform to test therapies that may rectify the contractile defects caused by cMyBP-C haploinsufficiency.
Abstract 16778: Effectiveness of Platelet Inhibition on Reducing High-Intensity Transient Signals to Cerebral Circulation During Tavi
Authors: Kalantzis Charalampos , Vavouranakis Michael , Kariori Maria , Voudris Vasilios , Toutouzas Konstantinos , Latsios Georgios , Kosmas Elias , Kalogeras Konstantinos , Moldovan Carmen-Maria , Bei Evangelia , Kolokathis Angel-Michail , Vrachatis Dimitrios , Siasos Gerasimos , Tousoulis Dimitrios , Vavuranakis Manolis
Published: April 2024

Introduction:
Despite the established dual antiplatelet treatment, embolic cerebrovascular events remain a major concern peri-operatively and following Transcatheter Aortic valve Implantation (TAVI). High Residual Platelet Reactivity (RPR) may contribute to platelet aggregation, propagating thrombosis on implanted materials. Therefore, we evaluated whether high RPR may predispose to an increased number of cerebrovascular emboli during the procedure.

Methods:
Consecutive patients who underwent transfemoral TAVI with Evolut™ R bioprosthesis were prospectively studied. Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor was administered to all patients 24 hours prior to the procedure at loading dose. The number of detected High Intensity Transient Signals (HITS) was assessed using Rimed Digi-Lite™ Transcranial Doppler on both cerebral arteries during the following phases of the procedure; Phase 0: 30 minutes prior to procedure initiation, Phase I: between access site puncture and introduction of the delivery system, Phase II: during the implantation of the bioprosthesis, until the removal of the delivery system. Platelet inhibition was measured prior to the procedure and expressed in PRU, using the VerifyNow® assay and defined as high RPR if PRU≥208.

Results:
Out of 28 total patients (81±7 years, 18 males (64%)), 12 patients (81±9 years, 8 males (66.7%)) had PRU ≥208 (high RPR group), while 16 patients (81±5 years, 10 males (62.5%)) had PRU<208 (low RPR group). All device implantations were performed without balloon pre-dilation. Among the high RPR group, a statistically significant higher number of HITS was recorded compared to the low RPR group (707±149 vs. 530±152, p: 0.004). This was mainly driven by the number of HITS detected during Phase II, compared to the rest procedure stages (247±84 vs. 165±28, p:0.004). A statistical significant correlation of PRU with the total number of HITS was found (r2: 0.25, p: 0.006).

Conclusions:
High RPR after dual antiplatelet loading resulted in larger burden of embolic HITS during TAVI. This may has implications for future strategies for cerebral embolic protection.
Abstract 16782: Effects of Epinephrine in Association With Anesthesia in Dental Intervention in Patients With Heart Failure. Results of the Double-Blind Controlled Trial (Teeth-HF Study)
Authors: Quaresma Sergio , Neves Ricardo , Giorgi Dante , Oliveira Maria , Neves Itamara , Grupi César , Bocchi Edimar A
Published: April 2024

Introduction:
The use of a local anesthesia solution with vasoconstrictor for the dental intervention of patients with heart disease is controversial since it could generate adverse cardiovascular risk. Also, its safety has not been investigated in patients with heart failure (HF).

Hypothesis:
The objective of this study was to evaluate the cardiovascular risk and pain score after dental intervention under local anesthesia with and without epinephrine, specifically tooth extraction and restoration, in patients with HF.

Methods:
Prospective, parallel group, controlled, double-blind study. Patients with HF, ejection fraction <45%, functional class II and III/IV and with optimized therapy were randomized to dental intervention using anesthesia solution lidocaine without epinephrine (LW) or anesthesia solution lidocaine with epinephrine (LE).

Results:
Seventy-two patients (50+/-10 years, 62% male, 27% ischemic) were randomized to LW (n=36) or LE (n=36). Systolic and diastolic blood pressure (BP) increased and maximum heart rate (HR) decreased significantly during intervention in relation to baseline phase in both groups (LW: BP, 120/79 to 125/82 mmHg and HR, 88 to 85 bpm, p<0.05; LE: BP, 116/75 to 124/78 mmHg and HR, 91 to 83 bpm, p<0.05). No differences were observed in BP, HR, arrhythmias and pain score before, during and after the dental intervention between the groups. However, it was observed a significant increase in the pain scale for the dental extraction in the LW group in comparison to the LE.

Conclusions:
Local anesthesia solution lidocaine with epinephrine seems to be safe and effective in patients with heart failure. This treatment did not cause adverse cardiovascular effects, and the pain score was lower in patients receiving LE in comparison with patients receiving LW. Patients with HF may benefit from the anesthesia solution with epinephrine for the dental intervention.
Abstract 16789: Pulmonary-Systemic Effective Arterial Elastance Ratio is Associated With Increased Adverse Outcomes in Advanced Heart Failure
Authors: Bruce-Mensah Araba , Bilchick Kenneth , Breathett Khadijah , Parker Alex , Mwansa Hunter , Tallaj Jose , McMillan Edward , Mazimba Sula
Published: April 2024

Introduction:
Advanced heart failure (HF) is characterized by ventricular arterial (VA) uncoupling and inefficient myocardial contractile mechanics. Effective arterial elastance (Ea) is a marker of total arterial load on the ventricle. There is paucity of data on the interaction between pulmonary-systemic effective arterial elastance (PSEa) [(Pulmonary systolic pressure/Stroke volume)/ (systolic blood pressure x 0.9)/Stroke volume)] with clinical outcomes in HF.

Hypothesis:
We hypothesized that increasing PSEa would be associated with higher adverse outcomes in patients enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial.

Methods:
Cox proportional hazards analysis and Kaplan Meier survival curves were used to assess associations between PSEa at end of pulmonary artery catheter (PAC) monitored therapy with clinical outcomes of time to death, transplant or LVAD (DTxLVAD) and time to death, transplant, LVAD or heart failure re-hospitalization (DTxLVADHF) over 6 months.

Results:
Among 165 patients (age 56.6 +/- 13.7 years, 29.1% female), the median PSEa ratio at the last PAC measurement was 0.48 (IQR 0.38 to 0.62). During 6 months of follow-up, PSEa ratio was significantly associated with the outcome of DTxLVAD in a Cox proportional hazards model (HR 2.18 per 0.25 increase in PSEa; 95% CI 1.41-3.37; P=0.0004), as well as the outcome of DTxLVADHF (HR 1.39 per 0.25 increase in PSEa; 95% CI 1.04-1.86; P=0.026); Kaplan-Meier curves demonstrated an increased rate of DTxLVAD in PSEa among patient in the highest quartile of PSEa (≥0.62) during follow- up period (Figure).

Conclusion:
PSEa is a novel marker of interventricular arterial coupling, that is associated with increased adverse events in advanced HF. These findings support further investigation of PSEa to guide risk stratification and prognosis in HF.