bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9301: The Association of Pulse Pressure With Brain Structure and Function in Healthy Individuals
Authors: Schumann Andy , de la Cruz Feliberto , Baer Karl-Juergen
Published: April 2024

Introduction:
Hypertension is associated to changes of structural and functional brain networks that lead to impairment of cognitive performance. Recently, pulse pressure (PP) has been suggested as cardiovascular risk factor in hypertension.

Hypothesis:
In this study, we tested whether elevated PP is accompanied by brain structural and functional changes in healthy individuals without hypertension.

Methods:
We investigated 115 healthy subjects (41±17 years, 55% females) without cardiovascular, neurological or psychiatric disorders. Structural and functional brain imaging was performed on a 3 Tesla Siemens Prisma. We assessed cognitive function using the MATRICS Consensus Cognitive Battery. Participants were categorized by PP in normal and high PP (PP>50 mmHg) according to resting blood pressure measurements in the laboratory. The normal PP group was reduced to match the high PP group with respect to age, gender, and education level. From resting functional brain images, we extracted whole-brain network connectivity between 260 independent brain regions to estimate global graph-theoretical features for integration (efficiency), resilience (assortativity), and segregation (clustering coefficient). Cortical thickness and volume were extracted from structural images using the Freesurfer image analysis suite.

Results:
While subgroups did not differ in terms of heart rate variability, baroreflex sensitivity was decreased in the high PP group. Furthermore, subjects with high PP performed worse in the trail-making task that primarily assesses processing speed (p<0.001, FDR-corr.). Graph theoretical analyses revealed that functional brain networks in subjects with high PP were less efficient, clustered and resilient than normal PP (all p<0.001, FDR-corr.). There were no differences in brain structure between groups. However, we found a negative correlation of PP with cortical thickness in the lateral prefrontal cortex over all subjects, suggesting that high PP is associated with cortical thinning in this area (corrected for age, gender and education).

Conclusion:
Elevated PP is associated with an altered organization of functional brain networks, lower cortical thickness and decreased processing speed in healthy subjects.
Abstract 9311: Heart Rate Modulates the Relationship of Augmented Systolic Blood Pressure With the Blood Natriuretic Peptide Levels
Authors: Tomiyama Hirofumi , Kazuki Shiina , Nakano Hiroki , Fujii Masatsune , Matsumoto Chisa , taka taka , Chikamori Taishiro , Yamashina Akira
Published: April 2024

Introduction:
Augmented central systolic blood pressure (cSBP), which is known to affect the cardiac afterload, is an independent risk factor for cardiovascular disease. While an inverse relationship is known to exist between the heart rate (HR) and cSBP, it has not yet been clarified if the HR also modulates the association between the cSBP and the cardiac afterload.

Hypothesis:
The present study was conducted to clarify whether the association of the cSBP with the serum levels of the N-terminal fragment B-type natriuretic peptide (NT-proBNP) differs between subjects with high and low HRs, using data obtained from the same subjects on two occasions (2009 and 2012) so as to confirm their consistency.

Methods:
The data analyzed in this study were the radial augmentation index (radial AI), systolic pressure at the second peak of the radial pressure waveform (SBP2), and serum NT-proBNP levels measured in a worksite cohort of 2000 middle-aged men in 2009 and in 2012.

Results:
For the purpose of this study, the subjects were divided into three groups by the HR (i.e., -69, 70-79, and -80 beats/minute). While the serum NT-proBNP levels were similar among the three groups, the radial AI increased and the SBP1-2 decreased significantly with decreasing HR (
P =
0.01). After the adjustment, the SBP2 showed a significant association with the serum NT-proBNP levels in the overall study population {Non-standardized co-efficient (B) = 0.005, Standard error (SE) = 0.001,
P
0.01 in 2009 (n = 2257), and B = 0.004, SE = 0.001,
P =
0.01 in 2012 (n = 1986)}. In subgroup analyses, the SBP2 showed a significant association with the serum NT-proBNP levels {B = 0.004, SE = 0.002,
P
=0.02 in 2009 (n = 1291) and B = 0.005, SE = 0.001,
P =
0.01 in 2012 (n = 1204)} only in the subject group with a HR of -69 beats/min.

Conclusions:
In middle-aged Japanese men, the relationship between the cSBP and the cardiac afterload appears to differ depending on the heart rate; the results of our analysis showed that the relationship between the cSBP and cardiac overload may be more pronounced and strongly significant in patients with low HRs as compared to patients with high HRs.
Abstract 9315: Mortality Risk Associated With Cessation of Mineralocorticoid Receptor Antagonists in Heart Failure Patients and Hyperkalemia; A Real-World Study From a Nationwide Administrative Database
Authors: Kohsaka Shun , Kikuchi Takashi , Mogalli Rashad , Ishizu Tomoko , Okami Suguru , Yajima Toshitaka
Published: April 2024

Introduction:
Mineralocorticoid receptor antagonists (MRAs) are guideline-directed therapy for improving clinical outcomes in heart failure (HF) patients. While maximum tolerated dose is recommended, MRA increases serum potassium (sK), leading to dose reduction or cessation. However, optimal threshold of sK level for MRA cessation or continuation in HF patients remains unclear. In this study, we assessed impact of MRA cessation on risk-benefit balance of hyperkalemic (HK) HF patients.

Methods:
A retrospective observational study was conducted using a Japanese hospital claim database (April 2008-September 2018). HK was defined as at least two sK ≥5.1 mmol/L within a 12-months interval. MRA cessation was defined as discontinuing MRA ≥ 30 days within 1 year from first HK episode. We examined relative mortality risk between hyperkalemic HF patients with or without MRA cessation by employing propensity score (PS) matching method. To evaluate risk-benefit balance between the two groups, cubic spline regression curve was generated by calculating mean hazard ratios (HR) in each sK strata.

Results:
Out of 15,442 hyperkalemic HF patients, we found 2,220 patients with MRA prescriptions (mean age, 77.77±10.95 years; follow-up period, 2.4±1.9 years). Cumulative incidence of MRA cessation and dose reduction was 52.7% and 6.5% at 1 year, respectively. In the PS matching analysis including HK patients, mortality rate was significantly higher in MRA cessation group compared to no cessation group (HR 1.21, 95% CI: 1.01-1.44, p=0.038). In cubic-spline analysis, increased relative mortality risk with MRA cessation compared to no cessation was observed in sK level below 5.7 mmol/L (Figure).

Conclusions:
We found a high MRA cessation rate amongst HF patients with HK, despite increased mortality risk in those with ceased MRA at sK level below 5.7 mmol/L in our real-world cohort. Careful consideration of risk-benefit balance is needed for MRA cessation in hyperkalemic HF patients.
Abstract 9317: Soluble Guanylate Cyclase Activator Treatment Improves Vasomotor Function in an Accelerated-Ageing Mouse Model
Authors: Ataei Ataabadi Ehsan , Golshiri Keivan , de Vries René , Brandt Renata M. C. , Van Der Pluijm Ingrid , Danser Jan H , SANDNER Peter , Roks Anton
Published: April 2024

Introduction:
Vascular ageing is a key driver of cardiovascular diseases. Mice with partial deletion of the repair enzyme gene
Ercc1
(

Ercc1
Δ/-

) display accelerated vascular ageing which is associated with decreased nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling, oxidative stress, inflammation, and cellular senescence. Restoring this pathway could be an effective treatment opportunity for vascular ageing. We therefore, investigated the therapeutic potential of the sGC activator BAY 56-6544, which can activate oxidized and heme-free sGC in

Ercc1
Δ/-

mice.

Design and Method:

Ercc1
Δ/-

and wild-type (WT) mice received either vehicle or BAY 54-6544 chow for 8 weeks. Blood pressure (BP) and
in-vivo
vasodilation (reactive hyperemia: RH) were measured at 15 and 16 weeks respectively. Mice were sacrificed at 17 weeks. Thoracic aorta (TA) endothelium-dependent (ED) and -independent (EI) relaxations were assessed (wire-myograph). Afterwards, we investigated the expression level of senescent markers
p16
and
p21
and inflammatory markers
Il-6
and
Ccl2
in aorta by qPCR.

Results:
BP was similar in all groups. RH was decreased in

Ercc1
Δ/-

vs. WT (P=0.03) and significantly improved after BAY 54-6544 treatment to the same level as in WT. In vehicle-treated

Ercc1
Δ/-

mice maximal NO-mediated relaxation in TA to acetylcholine (ED) and sodium nitroprusside (EI) were decreased as compared to WT (ED: 46.97±7.04 vs. 72.33±3.03, P=0.0001; EI: 75.47±5.27 vs. 88.30±3.64, P=0.02). Although BAY 54-6544 treatment did not improve ED response significantly, it improved EI relaxation in

Ercc1
Δ/-

to the same level as in WT (EI 88.54±3.26). EI response in BAY 54-6544-treated WT was the same as in vehicle-treated one (86.98±3.56). mRNA expression of
p16, p21
and
Ccl2
were significantly higher in vehicle-treated

Ercc1
Δ/-

, whereas BAY 54-6544 treatment could attenuate this increase.

Conclusion:
DNA repair deficiency in

Ercc1
Δ/-

mice causes a disruption of NO-sGC-cGMP signaling and a decrease of vasodilator response. Treatment with the BAY 54-6544 improved NO-mediated vasodilation and attenuated vascular senescence and inflammation markers. Thus, BAY 54-6544 could be a potential therapeutic treatment to attenuate vascular ageing.
Abstract 9322: Internal Medicine Resident Education Improves Cardiac Rehabilitation Knowledge, Attitudes, and Referral Rates
Authors: Torosyan Nare , Wang Maggie , Bairey Merz C , Wei Janet , Shufelt Chrisandra
Published: April 2024

Introduction:
Cardiac rehabilitation (CR) remains underutilized despite known benefits. Residency training may be an opportunity to address barriers to CR referrals, including physician knowledge gaps and unfamiliarity with referral processes. We sought to investigate the impact of resident education on knowledge and attitudes towards CR in a pilot study.

Methods:
Voluntary CR survey was sent to 20 internal medicine residents in a primary care clinic using an online-based platform. Following survey completion, residents received a scripted educational lecture and handout on CR. Surveys were redistributed 2 months post-education. Mean aggregate knowledge scores and attitude ratings on a 5-point Likert scale pre- and post-education were analyzed using paired t-tests. Referral rates of eligible patients 2 months pre- and post- education were analyzed using Fisher’s exact test.

Results:
Sixteen (80%) residents responded to both pre- and post-education surveys. Thirteen residents (81%) reported no education on CR within the past year. There was a significant increase in aggregate knowledge scores on CR components (5.1 ± 2.1 vs 7.0 ± 1.4,
p
= 0.001), insurance coverage (2.4 ± 1.8 vs 5.6 ± 0.7,
p
< 0.0001), and eligible diagnoses (7.1 ± 4.8 vs 9.9 ± 3.4,
p
= 0.03) following education (figure). Resident attitude ratings also improved after education, particularly in comfort level explaining CR (3.69 ± 1.30 vs. 2.06 ± 1.06,
p
< 0.0001) and familiarity with the referral process (4.00 ± 1.15 vs. 2.18 ± 1.11,
p
< 0.0001). CR referrals increased from 0% (0 out of 10 eligible patients) to 33% (3 out of 9 eligible patients) post-education (
p
= 0.09).

Conclusions:
Internal medicine resident knowledge and attitudes towards CR significantly improved after education and may play an important role in facilitating CR referrals. Future studies on optimizing strategies for incorporation of CR education into the residency curriculum is needed.
Abstract 9330: Machine Learning Can Enable the Automation of Clinical Endpoint Adjudication
Authors: Lea Halsey , Nampally Sreenath , Hutchison Emmette R , Stedt Christoffer , Järemo Andreas. , Persson Anders , Weatherall James , Khan Faisal M , Andersson Tomas , Khader Shameer , Dennis Glynn , Bhatt Deepak L , Steg Philippe G
Published: April 2024

Introduction:
Clinical Endpoint Adjudication is a critical component of Cardiovascular (CV) clinical outcome trials and relies on manual decision making to adjudicate clinical events, including CV death. This process is resource intensive and subject to human-driven variance. As part of a broader initiative to automate data collection and analysis of clinical endpoints, we evaluated whether machine learning (ML) algorithms could replicate the outcomes of expert adjudication for CV death. Algorithms were trained on data from THEMIS (NCT01991795), a large, randomized trial comparing ticagrelor to placebo in patients with Type 2 Diabetes Mellitus.

Methods:
We deployed a deep learning, biomedical named entity (NE) extraction model called BERN to extract relevant NE’s from clinical text of THEMIS events. NE’s were transformed into a sparse, numerical matrix and concatenated with event-level structured features to form a data set of 962 events. Expert adjudicator consensus for CV death was used as ground truth. We trained models using grid search and cross validation, experimenting with XGBoost, Random Forest, Logistic Regression, and Naïve Bayes. Performance was assessed on a 25% (240 of 962) validation subset of the data excluded from training. Metrics used to evaluate performance were Precision, Recall, Accuracy and Area Under the Receiver Operating Characteristic Curve (AUC).

Results:
Best performance was observed on models trained using Naïve Bayes (>97% ROC AUC on validation data), see Table. Top ranked features for classifying CV death included site investigator decision, sex, and NE’s associated with diagnoses or symptoms, such as “edema” and “chest pain.”

Conclusion:
With high consistency between automated and expert adjudication, our models demonstrate that machine learning may augment or even replace clinician adjudication in CV outcome trials. Subsequent research will focus on pursuing ML approaches to adjudicate other outcome events.
Abstract 9341: Hepatic Steatosis Index and Fibrosis-4 Scores in Patients With Type 2 Diabetes - Post Hoc Analyses from VERTIS CV
Authors: Corbin Karen D , Dagogo-Jack Samuel , Cannon Christopher P , Cherney David Z , Cosentino Francesco , McGuire Darren K , Shih Weichung J , Frederich Robert , Liu Jie , Lin Jianxin , Cater Nilo B , Pratley Richard E
Published: April 2024

Introduction:
Given the potential link between non-alcoholic fatty liver disease and increased cardiovascular (CV) risk, the associations between markers of hepatic steatosis/fibrosis with CV and kidney outcomes were explored.

Methods:
These post hoc analyses were conducted on data from the VERTIS CV trial that randomized patients with type 2 diabetes (T2D) and atherosclerotic CV disease (ASCVD) to ertugliflozin 5 or 15 mg or placebo, with all randomized groups pooled for the present analyses. The presence of hepatic steatosis was estimated by hepatic steatosis index (HSI; 8 х ALT/AST + BMI + 2 if T2D + 2 if female); and for hepatic fibrosis, fibrosis-4 score (FIB-4; [age х AST]/[platelets count х √ALT]). Patients were divided into quartiles (Q1 to Q4) according to baseline for each score. CV and kidney outcomes (CV death/myocardial infarction/stroke [MACE]; hospitalization for heart failure [HHF]/CV death; CV death; HHF; and sustained ≥40% decrease in eGFR from baseline/dialysis or transplantation/kidney death) were stratified by baseline HSI and FIB-4 quartiles.

Results:
Among 8246 patients, the mean age was 64.4 years, mean BMI 32.0 kg/m
2
, mean HSI 44.0, and mean FIB-4 score 1.34. Event rates of MACE, HHF/CV death, CV death, and HHF increased with FIB-4 quartile (
Fig A
). The hazard ratios (HR, 95% CI) of events by FIB-4 quartile (Q4 vs Q1) were 1.48 (1.25, 1.76), 2.0 (1.63, 2.51), 1.85 (1.45, 2.36), and 2.94 (1.98, 4.37) for MACE, HHF/CV death, CV death, and HHF, respectively. The kidney composite did not differ across FIB-4 quartiles. CV and kidney outcomes did not differ across HSI quartiles, except for higher incidence of HHF in the upper HSI quartile (HR [95% CI], Q4 vs Q1: 1.52 [1.07, 2.17]) (
Fig B
).

Conclusion:
In VERTIS CV, baseline fibrosis scores were associated with incident CV events in patients with T2D and ASCVD, despite the upper cutoff excluding advanced fibrosis. Steatosis only correlated with HHF, and neither measure was associated with the composite kidney outcome.
Abstract 9354: Socioeconomic, Demographic, and Geographic Trends in Mortality from Peripheral Artery Disease in the United States from 2000-2019
Authors: mously haytham , Kimura Stephen , Hammad Tarek , Shishehbor Mehdi H , Li Jun
Published: April 2024

Background:
Much is known about mortality trends in coronary artery disease (CAD) and cerebrovascular disease (CVD), yet data reporting mortality trends for peripheral artery disease (PAD) are scarce. We sought to explore overall PAD mortality trends in the US.

Methods:
The Multiple Cause of Death database from the Center for Disease Control was used to identify patients, aged 25 years and older, who died of PAD between years 2000 to 2019. Patients who died from PAD were identified using International Classification of Diseases 10th revision codes. Patient socioeconomic, demographic, and geographic factors were reported and analyzed. Age-adjusted rate were calculated using a standard population and reported in per-million persons (PMP). Finally, PAD mortality trends were compared to CAD and CVD.

Results:
A total of 854,616 PAD deaths were identified and showed decreasing mortality from 403 to 99 age-adjusted years PMP from 2000-2019. PAD mortality increased with increasing age (crude rate of 1.0 PMP vs 3806 PMP among 25-34 vs >85 year-olds respectively). PAD mortality was also higher among Black individuals from 2000 to 2006, but has equalized to the mortality rate of White individuals. PAD mortality was higher among men compared to women, but the gap has decreased over time. There was significant geographic state-level variation (3 fold) in PAD mortality, with large fringe metros demonstrating the lowest mortality. When compared to CAD and CVD, PAD mortality decreased by 75% from 2000 and 2019, compared with a 61% reduction in CAD mortality and a 46% reduction in CVD mortality (Figure 1).

Conclusion:
From 2000 to 2019, mortality due to PAD in the US has decreased at a much higher rate compared to CAD and CVD. Despite this trend, PAD remains a major cause of mortality in the US, disproportionately affecting elderly individuals, generally those living in less metropolitan areas, and men of both White and Black ethnicity, although differences in race and gender are diminishing.
Abstract 9364: Caregiver Anxiety Significantly Reduced from Baseline to 24 Months After Surgery: Findings from the Sustaining Quality of Life of the Aged: Heart Transplant or Mechanical Circulatory Support (
Sustain-it)
Study
Authors: Petty Michael , Wu Tingqing , Andrei Adin-cristian , Baldridge Abigail S , Warzecha Anna , Kao Andrew , Spertus John , Hsich Eileen M , Dew Mary Amanda , Pham Duc Thinh , Hartupee Justin , Cotts William , Pamboukian Salpy , Pagani Francis D , Lampert Brent , Johnson Maryl R , Murray Margaret A , Takeda Koji , yuzefpolskaya melana , Silvestry Scott , Kirklin James K , Yancy Clyde , Grady Kathleen L
Published: April 2024

Introduction:
We previously reported higher health-related quality of life (HRQOL), lower depression scores, and decreased anxiety in caregivers (CGs) of older (60-80 years) heart failure (HF) patients (PTs) treated with destination therapy mechanical circulatory support (DT MCS) or heart transplantation (HT) from baseline (before surgery) to 12 months post-surgery. We expand the analysis of CGs’ HRQOL and symptoms of depression and anxiety through 24-months post-surgery.

Methods:
From 10/1/15-12/31/18, 13 U.S. centers enrolled 301 CGs of HF PTs: 193 awaiting HT (92 with MCS, 101 without MCS) and 108 DT MCS. At baseline and 24-months post-surgery, CGs completed the following instruments: EQ-5D-3L (Visual Analog Scale [VAS]: 0 [worst]-100 [best] imaginable health state); PHQ-8 (range=0-24; score
>
10=current depressive symptoms); and STAI-State (range=20-80, higher score=more anxiety). Analyses included paired t-tests and baseline-adjusted linear regression.

Results:
CGs average age was 60.9±10 years, 85% were Caucasian, 85% female, and 83% spouses. No significant differences in HRQOL and depressive symptoms were found between groups at baseline, nor were significant changes observed between baseline and 24-months within any group. At baseline, anxiety was higher for CGs of DT MCS PTs compared to CGs of HT MCS (p=0.026) and HT non-MCS PTs (p<0.001; Figure). Between baseline and 24-months, STAI-State total scores were reduced among DT MCS and HT Non-MCS CGs (p=0.019 and p=0.001, respectively), but not among HT MCS CGs (p=0.86). At 24 months, significant between-group differences were observed in all scales: HRQOL was highest in HT non-MCS, depressive symptoms and anxiety highest in HT MCS CGs.

Conclusions:
Recognizing the impact of HT and DT MCS on CGs of older HF PTs may allow clinicians to provide targeted support to CGs, especially related to anxiety. These findings also may inform PT and CG decision making when considering surgical treatments for HF.
Abstract 9369: Nanoparticle-mediated Delivery of TT-10 Promotes Cardiomyocyte Proliferation and Myocardial Repair
Authors: Chen Wangping , Pretorius Danielle , Zhou Yang , Zhang Jianyi
Published: April 2024

The pharmaceutical product TT-10 increases cardiomyocyte proliferation and survival by upregulating nuclear levels of Yes-associated protein (Yap) and the expression of Yap-targeted genes. When evaluated in a mouse model of myocardial infarction (MI), intraperitoneal TT-10 administration was associated with improvements in infarct size and cardiac function 1 week after treatment, but functional parameters progressively declined at later time points [1]. Here, we tested our hypothesis that the potency of TT-10 for myocardial repair could be increased by loading it into poly-lactic-co-glycolic acid nanoparticles (NPs) before intramyocardial administration. Mice were treated with injections of DPBS (n=9), empty nanoparticles (Empty-NPs, n=8), TT-10 solution (TT-10-sol, n=8), or TT-10-loaded NPs (TT-10-NPs, n=9) immediately after MI was induced via permanent ligation of the coronary artery. Cardiac function was assessed via echocardiography, infarct size via histological Fast-Green staining, cardiac hypertrophy via measures of the heart-weight:bodyweight (HW:BW) ratio, cardiomyocyte proliferation via staining for Ki67 and phosphorylated histone 3 (PH3), and apoptosis via TUNEL. In vitro assessments confirmed that TT-10 was released from the TT-10-NPs for up to 4 weeks, and that the NPs were taken up by cultured cardiomyocytes. 1 and 4 weeks after MI induction and treatment, measures of left-ventricular (LV) ejection fraction (EF) and fractional shortening (FS) were significantly greater in TT-10-NP animals than in the TT-10-sol, Empty-NP, or DPBS groups; LV EF and FS also remained stable in the TT-10-NP group, while measurements in all other groups worsened (but not significantly), between the two time points. TT-10-NP treatment was also associated with significantly smaller (by ~20%, p<0.05) infarcts and significantly lower HW:BW ratios at Week 4; with significantly greater proportions of Ki67
+
, PH3
+
, and nuclear-Yap
+
cardiomyocytes at Week 1; and with significant declines in TUNEL
+
cardiomyocytes 72 hours after MI and treatment. Thus, NP-mediated delivery of TT-10 results in the efficacy of both the magnitude and durability of the benefits associated with promotion of myocyte proliferation in a mouse MI model.

[1]. PMID: 30456335
Abstract 9380: Rescuing Mitochondrial Fusion/Fission Balance Mitigates Oxidative Stress, Myocardial Injury and Apoptosis in Rats with Doxorubicin-induced Cardiotoxicity
Authors: Maneechote Chayodom , Khuanjing Thawatchai , Ongnok Benjamin , Arinno Apiwan , Prathumsap Nanthip , Chunchai Titikorn , Arunsak Busarin , Kerdphoo Sasiwan , Chattipakorn Siriporn , Chattipakorn Nipon
Published: April 2024

Introduction:
Doxorubicin (DOX) has been an extensively used chemotherapeutic drug in handling a wide range of cancers. Cardiotoxicity induced by DOX is a serious adverse effect of oncologic therapy. Although mitochondrial dynamic modulators including mitochondrial fission inhibitor (Mdivi-1) and fusion promoter (M1) have been shown as potential therapeutic remedies to treat various cardiovascular disorders, the cardioprotective effects of Mdivi-1 and M1 in DOX-induced cardiotoxicity is not known.

Hypothesis:
Mdivi-1 and M1 treatments reduce oxidative stress, myocardial injury, and programmed cell death by apoptosis, leading to improved left ventricular (LV) function in rats with DOX-induced cardiotoxicity.

Methods:
Male Wistar rats (n=20) were injected with either DOX (3 mg/kg, 6 doses, n=5) or 3% DMSO in NSS (n=5) as a control. In the DOX group, DOX-treated rats were received one of the following treatments: 1) 3% DMSO in NSS (n=5), 2) Mdivi-1 (1.2 mg/kg/day, n=5), 3) M1 (2 mg/kg/day, n=5). All treatments were given to the rats via intraperitoneal injection for 30 days beginning simultaneously with the first DOX injection. LV function, cardiac tissue malondialdehyde (MDA), serum cardiac troponin-I (c-TnI), and cleaved caspase-3 (CC3) protein levels were determined.

Results:
Injection of DOX markedly increased cardiac MDA, c-TnI, and CC3 levels (Fig. 1A-D). Impaired left ventricular ejection fraction (67% for DOX vs. 91% for control) was observed. Mdivi-1 and M1 co-treatment remarkably reduced the levels of MDA, c-TnI, and CC3, leading to increased LVEF from 67% in DOX to 89% in Mdivi-1 and 90% in M1, respectively (Fig. 1A-D).

Conclusions:
Mitochondrial fission inhibitor and fusion promoter effectively protected the heart from DOX-induced cardiotoxicity through suppression of oxidative stress, myocardial injury, and apoptosis. These findings indicate the mitochondrial dynamics as novel therapeutic targets in preventing Dox-induced cardiotoxicity.
Abstract 9388: The ALPACA Study, an EHR Based Analysis of the Association of Elevated Alkaline Phosphatase With Cardiovascular Events
Authors: Ambery Philip , Van-den-Broek Fe , Brookes-Smith Irena
Published: April 2024

Alkaline phosphatase (ALP) has a key role in vascular calcification, a process implicated in cardiovascular (CV) diseases. Previous studies suggest elevated ALP is associated with increased risk of CV events, and that this association is strengthened by elevated baseline bilirubin. The risk of CV events in patients with an acute coronary syndrome (ACS) event is yet to be explored. The analysis was performed on TriNetX, a federated EHR platform of 34 large HCOs in the US. Patients who had an ACS event in 2017-2018 and had an ALP recorded ±30 days were divided by ALP below or above 79 IU/L (approximately 38,000 patients), and ALP below 70 or above 121 IU/L (approximately 12,000 patients). Patients were propensity score matched on comorbidities, laboratory measures and medications. CV outcomes, non-CV outcomes, all-cause hospital admissions and mortality were estimated at 1 year post-ACS event using the Kaplan-Meier method. Elevated ALP was associated with atrial fibrillation and heart failure events. It was also associated with renal progression and infection but not with atherothrombotic events. On top of elevated ALP, elevated bilirubin levels were a key risk driver for these outcomes. Both markers were associated with re-hospitalization and all-cause mortality. This study has confirmed that elevated ALP is strongly associated with heart failure events, re-hospitalization and mortality in ACS patients. Further research on the association between ALP, bilirubin and cardiovascular outcomes is warranted.
Abstract 9394: Establishing Validity of a Midlife Black Women's Wellness Program
Authors: Jones Holly J , Butsch Kovacic Melinda , Bakas Tamilyn
Published: April 2024

Introduction:
Expert ratings and qualitative feedback are essential for establishing validity of materials developed for interventions. Validation of intervention content should be established prior to initiation of trials. In collaboration with a community research advisory board, the purpose of this study was to analyze expert ratings and qualitative feedback for the Midlife Black Women’s Stress Reduction Wellness (B-SWELL) intervention materials.

Methods:
The B-SWELL is a culturally tailored 8-week program that leverages stress reduction to lower cardiovascular disease (CVD) risk in midlife Black women by promoting the adoption of the AHA’s Life’s Simple 7 healthy lifestyle behaviors (LS7). Using community participatory methods, the LS7 metrics and B-SWELL binder were culturally tailored and targeted to midlife Black women. A multilevel mixed methods approach was used to establish content and face validity for the B-SWELL binder made up of eight modules. Twelve experts consisting of midlife Black women (n=6), researchers (n=3), and integrative health specialists (n=3) were purposefully recruited to rate each B-SWELL module and the overall binder for content accuracy, topic relevance, stress relevance, cultural appropriateness, feasibility, usefulness, ease of use, and appeal using a 5-point Likert scale (1 strongly disagree to 5 strongly agree). Open ended questions were integrated with ratings to obtain insight into areas needing improvement.

Results:
Combined mean expert ratings for individual B-SWELL modules were high with means ranging between 4.43 and 4.66. Group ratings differed for individual B-SWELL modules and the B-SWELL binder with midlife Black women having the highest mean ratings (4.71, 4.97), followed by researchers (4.56, 4.73), and integrative health specialists (4.11, 4.40). Narrative data provided details to guide refinement.

Conclusions:
The B-SWELL intervention materials exhibited strong evidence of content and face validity. Testing feasibility of the B-SWELL intervention in a future study is warranted, ultimately leading to a well-powered randomized control clinical trial to test efficacy of the B-SWELL in lowering CVD risk in midlife Black women through adoption of the LS7 healthy lifestyle behaviors.
Abstract 9802: Social Determinants of Health and Cardiovascular Risk Among Adults with Diabetes: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Zhang Lisa , Reshetnyak Evgeniya , Pinheiro Laura , Cummings Doyle M , Carson April P , Durant Raegan W , Malla Gargya , Safford Monika
Published: April 2024

Introduction:
Social determinants of health (SDOH) have been associated with diabetes risk; however, their association with cardiovascular disease (CVD) events in individuals with diabetes is unknown. We hypothesized that as the number of SDOH among individuals with diabetes increased, the risk of CVD events would also increase.

Methods:
The REGARDS study is a national, biracial cohort of 30,239 individuals ≥45 years old recruited in 2003-7. We included 6,322 participants with diabetes at baseline, defined as healthcare professional diagnosis, diabetes medication use, or blood glucose values (fasting ≥126 or random ≥200 mg/dl). The outcome was CVD events, a composite defined as expert adjudicated myocardial infarction (MI), stroke, or fatal coronary heart disease (CHD) with follow up through 2018. Guided by the Healthy People 2030 framework, we included 5 SDOH significantly associated with CVD events: < high school education, annual household income <$35,000, residing in a zip code with ≥25% poverty, no health insurance, and social isolation from friends/family. We used Cox proportional hazard models to examine associations between number of SDOH (0, 1, or ≥2) and the composite endpoint and each individual endpoint separately, adjusting for demographics, medical conditions, health status, and physiological factors.

Results:
The mean age was 66 ± 9 years, 53% were female, and 58% were Black. In a fully adjusted model, the presence of
>
2 SDOH significantly increased the risk of CVD events (HR 1.17 [95% CI 1.01-1.36]) (Figure). However, there was no association for MI, an association for stroke, and a graded association for fatal CHD (1.44 [1.07-1.93] for one SDOH; 1.64 [1.20-2.23] for
>
2 SDOH).

Conclusions:
Having ≥2 SDOH was independently associated with an increased risk of CVD events in individuals with diabetes, a finding driven by stroke and fatal CHD. Identifying individuals with diabetes who have ≥2 SDOH may help detect those at higher risk for stroke and CHD death.
Abstract 9806: Cardiac Remodeling Post Transcatheter Aortic Valve Replacement: A Comparison Between Veteran and Non-Veteran Populations
Authors: Jarsania Dhairya , Meyer Jonathan , Twing Aamir , Gokhale Sanket , Slostad Brody D , Dickens Helena , Groves Elliott , Kansal Mayank M , Shroff Adhir R
Published: April 2024

Background:
Transcatheter aortic valve replacement (TAVR) is increasingly utilized in the treatment of aortic valve disease. We assess echocardiographic changes over time to evaluate cardiac remodeling following TAVR between Veteran (VA) and non-VA populations.

Methods:
Retrospective analysis of 121, single operator TAVR procedures completed between March 2018 and June 2020 at the University of Illinois Hospital in Chicago, IL. Patients included those referred from the affiliated Jessie Brown Veteran Affairs hospital with the following inclusion criteria: transthoracic echocardiogram (TTE) at baseline and 6-month follow-up. Chi-Square tests were used to analyze categorical variables, paired t-tests for continuous variables, and multivariate analysis for subgroups.

Results:
One hundred and fifteen patients (VA: 59, non-VA: 56) were included in this study. The population had a mean age of 77.0 vs 73.2, BMI of 28.2 vs 30.4, 96.6% vs 56.6% male (p<0.001), and 57.6% vs 33.9% White (p=0.011) between VA and non-VA patients respectively.

Overall, there was no significant difference in chamber dimensions, LVEF, and RVSP; however, there was a significant decrease in wall thickness. Multivariate subgroup analysis showed no significant difference between groups except for RVSP.

Conclusion:
Overall, our study shows positive cardiac remodeling post TAVR, but there is no significant difference when comparing VA to non-VA populations. Although additional studies with larger sample sizes are warranted, the lack of disparity between these subgroups is reassuring.
Abstract 9810: Acute Exposure to Vaping E-Liquid Induces Multiple Cardiotoxic Effects on Fetal-Like Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Epicardial Cells
Authors: Ho Miriel , Ho Mirabelle , Librach Clifford
Published: April 2024

Introduction:
Cardiomyocytes (CM) and epicardial (EPI) cells are key to orchestrating proper heart development. Vaping during pregnancy is rising, however, its implications on the prenatal heart are not fully understood. We exploited the immature phenotype of human induced pluripotent stem (iPS)-derived CM (iCM) and EPI (iEPI) cells to investigate the acute effect of e-cigarette liquid (e-liquid) on early cardiogenesis.

Hypothesis:
E-liquid exposure triggers dysfunction in fetal-like cardiac cells via distinct mechanisms.

Methods:
Human iCM and iEPI cultures were exposed to heated e-liquid for 20 minutes, twice daily, for 3 weeks; controls were performed in parallel. Video microscopy monitored morphological alterations and contractions. Immunostaining/flow cytometry of cell markers, Annexin V, EdU incorporation quantified protein expression, cell viability and proliferation, respectively. Mean fluorescence intensity measured reactive oxygen species (ROS). Wound healing assays assessed cell migration. Data reported as mean±SD (n=4/study).

Results:
Human iPSCs were differentiated into cTnT
+
iCM and Wt1
+
iEPI cells with ≥83% purity. Addition of e-liquid progressively pruned the iCM syncytium, and slowed contractions in small regions from day 12. E-liquid treatment dysregulated HIF1α/p53 signaling in iCM relative to control. This enhanced apoptosis (49±5% vs. 21±6%) and disrupted G
1
/S cell cycle progression (5±1% vs. 15±3% in S-phase). Sustained elevation of ROS production by 35±7% led to ~20% decline in NKX2.5
+
progenitors (p<0.05 for all). E-liquid treatment also impaired iEPI motility (77±5% vs. 30±7% of open wound area), and reduced the proportion of iEPI-derived PFGFRβ
+
pericytes and αSMA
+
smooth muscle cells by ≥31% (p<0.05 for all). This was attributed to N-cadherin repression and E-cadherin upregulation, which promoted defective epicardial epithelial-to-mesenchymal transition that affected vascular mural cell differentiation.

Conclusions:
Acute e-liquid exposure is detrimental to iCM and iEPI cell survival, behavior and fate trajectories. Our study suggests that long-term maternal vaping may compromise fetal cardiovascular integrity and maturation, heightening the risk of developing congenital heart disease.
Abstract 9816: Clinical and Pathophysiological Relevance of Follistatin-Like 1 in Calcific Aortic Valve Disease
Authors: Chen Zhongli , Zhang Qianru , Zha Qing , Yu Chenxi , liu yan , Yang Ke
Published: April 2024

Introduction:
CAVD is a progressive disease resulting in severe aortic valve stenosis. Recent studies unveiled protective effects of FSTL1 in various cardiovascular disorders. But its role in CAVD is uncertain. This study aims to evaluate the clinical and pathophysiological relevance of FSTL1 in CAVD.

Methods:
FSTL1 level was measured in blood samples fromCAVD (n = 343) and non-CAVD (n = 318) patients. The diagnosis of CAVD was based on the echocardiography report. ApoE-/- mice and primary aortic valve interstitial cells (VICs) were used as animal and cell models respectively for mechanistic studies.

Results:
Compared with non-CAVD group, CAVD patients exhibits lower circulating FSTL1 concentrations [Median (IQR) ng/mL: 0.91 (0.52-1.50) versus 0.78 (0.34-1.25), p=0.002]. Multivariate logistic regression indicates that circulating FSTL1 level is independently associated with CAVD (OR: 0.831, 95% CI: 0.755-0.915, p<0.001) after full adjustment. Moreover, there is a non-linear relationship with threshold effect between FSTL1 level and CAVD: Below the turning point (FSTL1= 1.2ng/mL) the predicted probability of CAVD decreases significantly as FSTL1 level increases, but above 1.2ng/mL, the downtrend levels off. In ApoE-/- mice, overexpression of FSTL1 significantly reduces calcified nodule formation and structural remodeling of aortic valves. Finally, rhFSLT1 significantly alleviates calcium deposits, alkaline phosphatase activity, suppresses expression of osteogenic markers (BMP2, RUNX2, and MSX2) and inhibits phosphorylation of ERK1/2 in VICs in the osteogenic medium

Conclusion:
FSTL1 emerges as an important marker exhibiting inverse clinical association with CAVD and it alleviates the mineralization of murine valve and VICs. Further evaluation and manipulation of FSTL1 might provide a novel potential therapeutic opportunity for CAVD.
Abstract 9820: WATCH-DM Risk Score is Associated with Functional Capacity and Prognosis in Diabetic Patients with Heart Failure with Preserved Ejection Fraction
Authors: Iwakura Katsuomi , Onishi Toshinari , Okada Masato , Tanaka Nobuaki , Koyama Yasushi , OKAMURA ATSUNORI , Fujii Kenshi , Seo Masahiro , Yano Masamichi , Hayashi Takaharu , Nakagawa Akito , Nakagawa Yusuke , Tamaki Shunsuke , Yamada Takahisa , Yasumura Yoshio , Hikoso Shungo , Sotomi Yohei , Sakata Yasushi ,   The OCVC-Heart Failure Investigators
Published: April 2024

Introduction:
The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF) is frequent and associated with a higher mortality. WATCH-DM risk score is recently developed to predict the risk of HF among patients with T2DM using a machine learning approach (Segar et al, Diabetes Care 2019).

Hypothesis:
We hypothesized that WATCH-DM risk score would be associated with functional capacity and clinical outcomes in diabetic patients with HF with preserved ejection fraction (HFpEF).

Methods:
The PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study is a multicenter registration of patients hospitalized for acute decompensated HFpEF. Among 1095 patients registered between 2016 and 2020, 418 patients (38.2%) had T2DM (male gender 49.5%, age 80±9 years, HbA1c 6.8±1.0%). WATCH-DM risk score was calculated in each patient, using BMI, age, systolic/diastolic blood pressure, serum creatinine, HDL-C, fasting plasma glucose, QRS duration, history of myocardial infarction or coronary bypass graft, and patients were divided as the low to average (≤10 points), high (11-13 points) and very high (≥14 points) risk groups. We measured 6 minute walk distance (6MWD) and NT-proBNP before discharge. We followed the study patients for median of 386 days (IQR 221 to 729 days) to observe the major adverse cardiovascular events (MACE; composite of death, heart failure hospitalization and stroke).

Results:
The WATCH-DM score in the study patients were 12.8±3.1 points, and 108 patients (25.8 %) had low-average, 147 patients (35.2%) high, and 163 patients (39.0%) very high HF risk. There was significant difference in 6MWD (p=0.004) among the groups, and the low-average risk group had significantly longer 6MWD than the high risk group (p=0.049). NT-proBNP was lower in the low-average risk group than in other 2 groups. Cox proportional hazard model selected the WATCH-DM score as an independent predictor for MACE (p=0.006). Kaplan-Meier curve demonstrated that patients with the low-average risk had significantly lower incidence of MACE than the others (p=0.049).

Conclusions:
The WATCH-DM risk score predicted functional capacity and prognosis in diabetic patients with HFpEF.
Abstract 9826: Impact of Ischemic Heart Disease on Inpatient Outcomes of Atrial Fibrillation
Authors: Jamal Shakeel , Hassan Jawad , Kichloo Asim , Ijaz Sardar H , mahmoud mona , Ajmal Muhammad , Paul Timir K. , Bailey Beth
Published: April 2024

Introduction:
Comparative outcomes of hospitalizations for Atrial Fibrillation (AF) with and without coexisting ischemic heart disease (IHD) have limited large scale data. Coexistence of AF and IHD is common and exposed patients are at high risk for ischemic/hemorrhagic events. We assess baseline characteristics and outcomes in these hospitalized patients using National Inpatient Sample (NIS).

Hypothesis:
Ischemic heart disease worsens the inpatient clinical outcomes of atrial fibrillation.

Methods:
We conducted a retrospective analysis of hospitalizations for AF using data from NIS between 2013 and 2014. International classification of diseases, 9th revision was used to identify the target population. The primary outcome was inpatient mortality, hospital length of stay and cost.

Results:
A total of 1531704 hospitalizations for AF were identified, of these, 863, 352 hospitalizations were without IHD and 668, 342 hospitalizations were with secondary diagnosis of IHD. AF with IHD cohort was older (mean age, 76.4 vs 74.4, p <0.001), had low proportion of females (41% vs 55%, p <0.001), higher proportion of whites (83.4% vs 81.6%, p <0.001) and high comorbidities such as hypertension, diabetes mellitus, chronic kidney disease and congestive heart failure. AF with IHD had significant higher inpatient mortality (OR 1.02, CI 1.01-1.04), increased length of hospital stay (6 vs 5.8 days, mean difference 0.05, p <0.001) and higher cost of hospital stay (mean difference, 7122 USD, p <0.001). There was higher prevalence of cardiogenic shock (OR 2.97, CI 2.86-3.09), cardiac arrest (OR 1.58, CI 1.53-1.62), complete heart block (OR 1.46 (CI 1.40-1.53) and acute kidney injury (OR 1.10, CI 1.09-1.11) in AF with IHD cohort.

Conclusion:
AF with coexisting IHD is associated with higher inpatient mortality, increased cost of hospital stays, and prolonged length of hospital stay as well as higher comorbidity burden.
Abstract 9827: Impact of Standard Interventions for Dyslipidemia and Elevated Blood Pressure in Childhood Cancer Survivors
Authors: Javalkar Karina , Huang Yisong , Lyon Shannon , Palfrey Hannah , Hartz Jacob , Chen Ming Hui , De Ferranti Sarah D
Published: April 2024

Introduction:
Childhood cancer survivors (CCS) have an increased risk of premature cardiovascular disease (CVD). Whether they respond equally well to guideline-directed lifestyle and pharmacologic interventions for elevated BP, BMI, and dyslipidemia as those without history of childhood cancer is unknown. We hypothesized that CCS may have impaired response to these interventions when compared to controls.

Methods:
This retrospective case-control study included CCS and 3:1 age- and sex-matched controls treated in Boston Children’s Hospital Preventive Cardiology (2010-2019) using a quality improvement protocol based on NHLBI 2011 guidelines. Change in body mass index (BMI), blood pressure (BP), and lipids from baseline to follow-up were compared between groups using Mann-Whitney and regression analyses in SPSS.

Results:
We included 62 CCS and 186 controls. Both groups had a median age of 16 years and were 63% female. Among CCS, 46% received anthracycline and 71% received radiation. CCS and controls did not significantly differ in BP or BMI, total cholesterol, or LDL-C at baseline. CCS had higher fasting triglycerides (p<0.001) and lower HDL-C (p<0.001) than controls at baseline. Median follow-up time was 18 weeks. CCS had greater improvement in fasting triglycerides than controls (median -50 mg/dL vs. -0 mg/dL, p=0.003), even after adjusting for BMI (p=0.016). Change in BMI, LDL-C, and HDL-C did not significantly differ between groups. Approximately 35% of CCS had elevated BP at both baseline and follow-up, while elevated BP among controls decreased from 55% to 40% (p=0.036) (Figure 1).

Conclusions:
CCS demonstrated greater improvement in triglycerides compared to controls in response to standard interventions, but similar change in regard to other lipid parameters and BMI. In contrast, BP was less likely to improve in CCS compared to controls. Further study is needed to determine if more aggressive interventions are needed for CCS with elevated BP.