bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4141043: Upregulation of Dynamin 2 (DNM2) Increases Mitochondrial Fission and Cell Proliferation in Pulmonary Arterial Hypertension
Authors: Das Gupta Asish , Chen Kuang-Hueih , Wu Danchen , Lima Patricia , Martin Ashley , Mewburn Jeffrey , Al-Qazazi Ruaa , Emon Isaac , Colpman Pierce , Yerramilli Siddartha , Jones Oliver , Hindmarch Charles , Potus Francois , Bonnet Sebastien , Archer Stephen
Published: November 2024

Introduction:
Mitochondrial fission is mediated by dynamin related protein-1 (Drp1) activation; however, to complete fission, we have evidence that Drp1 requires assistance from the GTPase dynamin 2 (DNM2).

Hypothesis:
DNM2 interacts with Drp1 to regulate mitotic fission and cell cycle progression, permitting the hyperproliferative phenotype of pulmonary artery smooth muscle cells (PASMC) in pulmonary arterial hypertension (PAH).

Methods:
Colocalization of Drp1 and DNM2 was assessed using STED super resolution confocal microscopy. Interaction of Drp1 and DNM2 was confirmed by immunoprecipitation. The role of DNM2’s GTPase domain in mitochondrial targeting was assessed by heterologous expression of truncated constructs. Changes in transcriptomic signature from silencing DNM2 in PAH human PASMC (hPASMC) were measured by RNA-seq. DNM2 expression in control vs PAH was quantified in hPASMC (n=4-5/group) and lungs from human (n=5/group), monocrotaline (MCT) (n=4-5/group) and SU5416/hypoxia (Su/Hx) (n=4-5/group) induced rodents using immunoblots, immunohistochemistry and immunofluorescence. DNM2’s effects on cell proliferation, cell cycle and apoptosis were assessed by flow cytometry. siDNM2 was nebulized to rats with established MCT-PAH.

Results:
DNM2 is significantly increased in human and rodent PAH and silencing DNM2 reduces mitochondrial fission and cell proliferation and induces apoptosis and cell cycle blockade in the G0/G1 phase in PAH PASMC. DNM2 and Drp1 interact at mitochondrial fission sites. DNM2’s translocation to the mitochondria is Drp-dependent and requires DNM2’s GTPase domain. Silencing DNM2 downregulates the Regulator of Cell Cycle,
RGCC
. Augmenting DNM2 in normal PASMC induces mitochondrial fission and cell proliferation. miR-124-3p, which negatively regulates DNM2, is decreased in PAH PASMC. Augmenting miR-124-3p decreases DNM2 expression, inhibits fission and proliferation and induces apoptosis in PAH PASMC. Silencing STAT3 (also negatively regulated by miR-124-3p) reduces DNM2 and inhibits fission. siDNM2 regresses PAH in MCT-PAH rats.

Conclusion:
DNM2 binds to Drp1 and translocates to mitochondria, regulating fission. A pathological increase in DNM2 expression, driven by decreased miR-124a-3p and STAT3 activation, increases mitochondrial fission, proliferation and inhibits apoptosis in PAH PASMC. DNM2 regulates cell proliferation via RGCC. DNM2 is a fission mediator and its regulatory pathway offers potential PAH therapeutic targets.
Abstract 4141050: Calcium to Cross-Bridge Coupling within Intact in vivo Hearts Elucidated by Simultaneous Intracardiac Pressure and Intra-Cardiac Myocytes Calcium Measurements
Authors: Hale Joshua , Ellankil Laticia , Nguyen Kaycee , McAlister Lilly , Tugwell Katherine , Kwon Yunwoo , Tong Carl
Published: November 2024

Background:
Elucidating key mechanisms of cardiac contraction/relaxation can lead to new treatments for heart failure. Intact papillary muscles produce maximum force at much lower [Ca
2+
] than de-membraned cardiac tissue and show [Ca
2+
] to force hysteresis relationship. We then hypothesize that cross-bridge (CB) attachments sustain force generation independent of [Ca
2+
] after [Ca
2+
] enabling as a key driver of contraction.

Methods:
We acquired transgenic mouse model with cardiac myocyte specific endogenous fluorescent calcium sensor GCaMP8. GCaMP8 is green fluorescent protein coupled with calmodulin. We made a novel system using commercial parts and in-house software that can quantify GCaMP8-[Ca
2+
] fluorescence of
in vivo
beating heart. We then made simultaneous intra-cardiac pressure and [Ca
2+
] measurements of
in vivo
beating hearts.

Results:
By echocardiography, GCaMP8 hearts demonstrated similar size, reduced left ventricular ejection fraction, slowed maximal myocardial contraction velocity S, similar maximal myocardial relaxation velocity e’, and similar E/e’ ratio in comparison to WT. Thus, GCaMP8 hearts have depressed systolic function but preserved diastolic function. Western blotting did not show any expression differences in SERCA2a or phospholamban. Simultaneous intracardiac pressure and [Ca
2+
] measurements showed peak [Ca
2+
] occurring well before peak pressure. Normalizing delay to adjust for different heart rates, peak pressure occurs at 19%±3%SD delay from peak [Ca
2+
] of heart-beat duration, p<0.0001 n=5. Plot of [Ca
2+
]
vs.
pressure showed hysteresis relationship where pressure rises to peak as [Ca
2+
] falls after initial concordant rise. Pressure rises to only 48%±5%SD of peak at peak [Ca
2+
], p<0.0001 n=5.

Conclusions:
We demonstrated CB attachment sustains contraction independent of [Ca
2+
] within beating
in vivo
hearts. Unlike systole, calcium chelation has little impact on diastolic function. Modulation of CB function can be a new treatment class.
Abstract 4141076: Shared Genetic Characteristics and Molecular Mechanisms between Atrial Fibrillation and Aortic Valve Calcification: Insights from Transcriptome Data
Authors: Xiao Yichao , Qin Mali , Li Zhenyu , Liu Qiming , Zhou Shenghua
Published: November 2024

Background:
Atrial fibrillation (AF) is often linked to aortic valve calcification (AVC), leading to compromised valve elasticity and increased morbidity. Although clinically overlapping, the molecular interplay between AF and AVC has not been well elucidated. This study aimed to dissect the genetic and regulatory landscape of AF and AVC to identify potential therapeutic targets.

Methods:
We systematically retrieved genes related to AF and AVC from databases and clinical datasets. Intersection analysis identified common genes, followed by differential expression analysis, Gene Ontology (GO) enrichment, protein-protein interaction (PPI) network construction, and transcription factor (TF) regulatory network analysis.

Results:
Enrichment analyses revealed ten genes common to both AF and AVC, revealing their involvement in multiple pathways. PPI analysis highlighted six hub proteins: FCGR3A, S100A12, MNDA, S100A8, NCF2, and CASP1. The key transcription factors ETS1 and SPI1 were found to regulate these common genes, underpinning distinct TF-gene and TF-miRNA networks.

Conclusion:
This study identified key genes and transcription factors, including FCGR3A, MNDA, S100A8, S100A12, ETS1, and SPI1, that are central to both AF and AVC. Our findings offer insights into their molecular connections and propose avenues for further research and therapeutic intervention.
Abstract 4141098: Prognostic value of Achilles tendon assessment by ultrasonography to predict complexity of coronary artery disease in patients with acute coronary syndrome
Authors: FUJIOKA SHIMPEI , Shishikura Daisuke , Michikura Masahito , Morita Hideaki , Harada-Shiba Mariko , Hoshiga Masaaki
Published: November 2024

Background:
One of the major causes of atherosclerotic cardiovascular diseases is high low-density lipoprotein cholesterol (LDL-C) levels and prolonged exposure to high LDL-C can lead to the formation of atheromatous lesion. Achilles tendon thickening (ATT) is also known to be due to exposure to high LDL-C from the childhood in familial hypercholesterolemia (FH) and is one of the criteria for the diagnosis of FH in Japan. We have reported that ATT can be measured more accurately by ultrasonography（US-ATT）than X-ray（Xp-ATT）. The US-ATT in FH patients correlate with the severity of coronary artery disease; however, it is unknown whether the US-ATT correlates with the severity of coronary artery disease in non-FH patients. In this study, we investigated whether the evaluation of US-ATT could serve as a predictive indicator for the severity of coronary artery disease in non-FH patients.

Methods:
We investigated 95 consecutive patients who presented with acute coronary syndrome (ACS) at Osaka Medical and Pharmaceutical University Hospital from April 2023 to May 2024. ATT was measured by ultrasonography and radiography. The complexity of coronary artery disease was evaluated using the Syntax score and the number of coronary artery lesions with >50% diameter stenosis. FH diagnosis was based on clinical findings. Excluding FH patients, the relationship between the complexity of coronary artery disease and the mean of the right and left US-ATT as the mean US-ATT was evaluated.

Results:
The mean age of the patients was 67.7 years, and 81.9% were male. There were 10 patients with FH and 85 patients with non-FH. The mean US-ATT was 5.1 ± 0.6 mm. The mean US-ATT was associated with coronary multiple vessel disease in non-FH patients (p = 0.029). The association between the mean US-ATT and Syntax score was observed in non-FH patients (p = 0.031). The correlation between ATT and Syntax score was found to be stronger for US-ATT than Xp-ATT (p < 0.001 and p = 0.009). Multivariate analysis adjusting for age, gender, smoking, and HbA1c revealed that the mean US-ATT was an independent predictor of severe coronary artery disease (OR: 5.4, 95% CI: 1.45-20.2, p = 0.001).

Conclusions:
Even in non-FH patients, US-ATT was significantly associated with the complexity of CAD and showed a significant correlation. Given its greater accuracy, simplicity, and lack of radiation exposure, US-ATT could serve as an alternative method to predict severe CAD.
Abstract 4141101: Loss of Chondroitin Sulfate N-acetylgalactosaminyltransferase-2 (ChGn-2) Impairs Thrombus Resolution in Mice Model
Authors: Adinata Aditya , Hara Tetsuya , Achyar Arinal Chairul , Hirata Ken-Ichi , Emoto Noriaki
Published: November 2024

Background:
Deep vein thrombosis (DVT) remains a significant health problem where current therapy management still possesses risks. Thrombus resolution during natural DVT progression involves various leukocyte influx and pro-inflammatory responses. Chondroitin sulfate glycosaminoglycans (CS-GAGs), linear polysaccharides found on blood vessel endothelium and leukocyte cell surfaces, have been reported to regulate leukocyte trafficking in several inflammatory diseases. Furthermore, GAG chain function depends on the alteration in GAG chain length or sulfation. One of the involved enzymes is Chondroitin Sulfate N-acetylgalactosaminyltransferase-2 (ChGn-2), an enzyme which is able to elongate GAG chain. In humans, the ChGn-2 gene is expressed widely, implying that ChGn-2 might play roles in various mechanisms throughout the body. Nonetheless, ChGn-2 role in the pathology of DVT remains unclear.

Methods and results:
We investigated ChGn-2 role in DVT by completely ligating the inferior vena cava in 10 – 12-week-old male C57BL/6J mice (n = 25) and mice with global deletion of ChGn-2 (n = 25). We found a higher thrombus burden (p<0.0001) in day 4 and day 7 after surgery with a slower thrombus organization in the transgenic mice by Carstair staining in day 2 (p<0.05) and day 4 (p<0.01). Interestingly, loss of this gene also reduced MMP activity (p<0.001) in day 7 along with pro-inflammatory cytokines and leukocyte markers. Moreover, immunohistochemistry staining also showed that leukocytes were mostly found at the edge of the thrombus in the transgenic mice. Further examination by in vivo imaging of femoral vein ligation revealed an impaired leukocyte influx in the transgenic mice. Transferring leukocytes from WT mice into transgenic mice rescued the phenotype, while the reverse experiment led to an impaired leukocyte influx. Finally, simultaneous imaging of WT and ChGn-2 KO leukocytes revealed that WT leukocytes could infiltrate inside the thrombus but not ChGn-2 KO leukocytes, confirming that ChGn-2 in leukocytes is important in our study..

Conclusion:
Insufficient CS-GAGs length caused by the loss of ChGn-2 impaired thrombus resolution due to reduced leukocyte infiltration.
Abstract 4141103: Impact of Atrial Fibrillation and Atrial Fibrillation Therapies on Sports Performance in Female vs Male Athletes
Authors: Khan Ali , Lee Hyon Jae , Hills Mellanie , Moss Melissa , Lara Brenna , BAUMANN RAYMOND , brandt cynthia , Lampert Rachel
Published: November 2024

Introduction:
Atrial fibrillation (AF) decreases sports performance in athletes, and ablation is associated with a greater improvement in performance compared to medication. Endurance sports predispose males to AF more than females. However, once AF develops, it is unknown whether its impact in female athletes differs from that of males.

Aims:
To investigate the impact of AF and AF treatments in female versus male athletes.

Methods:
An internet-based survey, initiated via StopAfib.org, queried the impact of AF and treatment modalities on sports performance, training, and symptoms. Responses were categorized by reported sex. Reported performance (rated in comparison to personal best), frequency of training, and competition engagement were compared before the onset of AF symptoms versus when symptoms were at their worst, between males and females. These outcomes were similarly compared in relation to participants’ AF treatments.

Results:
Between 5/13/2019 and 2/29/2020, 219 female and 772 male athletes, 40% of whom were less than 60s years old, answered the survey. Development of AF was associated with declining reported sports performance, competition, and training frequency, with no significant difference between genders. Ablation in both males and females was associated with greater reported improvement in sports performance than the use of medications. Among 141 female athletes and 509 male athletes who have taken medication currently and/or in the past, 52% and 40% reported side effects, respectively. The most prevalent side effects for both males and females were fatigue/low energy and decreased athletic performance.

Conclusion:
Once AF develops, the impact on decreasing sports performance is similar in females and males. Both genders similarly reported more improvement with ablation than medications, which were frequently and similarly associated with side effects for females and males.
Abstract 4141141: Obesity is Associated with Impaired Angiogenesis in Patients with Heart Failure with Preserved Ejection Fraction
Authors: Frljak Sabina , Poglajen Gregor , Zemljic Gregor , Cerar Andraz , Sever Matjaz , Vrtovec Bojan
Published: November 2024

Background:
Obesity was associated with cardiac vessel remodelling, microvascular rarefaction, and poor angiogenetic response in patients with metabolic syndrome.

Aim:
Since myocardial microvascular damage may represent a key parameter in the pathogenesis of heart failure with preserved ejection fraction (HFpEF) we sought to investigate a potential correlation between obesity and parameters of angiogenesis in HFpEF patients.

Methods:
We enrolled 30 consecutive HFpEF patients with NYHA class III, left ventricular ejection fraction (LVEF) >50%, E/e' >15, and NT-proBNP >300 pg/ml. In all patients, endothelial progenitor cells (EPCs) were mobilized by granulocyte-colony stimulating factor (G-CSF; 10 mcg/kg, 5 days) and collected via apheresis. Before EPC mobilisation we performed echocardiography and measured plasma levels of biomarkers of angiogenesis. At the time of enrolment, obesity was defined as BMI >27 kg/m
2
.

Results:
Obesity was present in 17 patients (57%; Group A) and absent in 13 patients (43%; Group B). The groups did not differ in age (62±8 years in Group A vs. 61±7 years in Group B, P=0.65), gender (male: 76% vs. 77%, P=0.97), serum creatinine (1.06±0.24 mg/dL vs. 1.05±0.42 mg/dL, P=0.52), LVEF (58±8% vs. 59±5%, P=0.56), or E/e’ (21.4±4.0 vs. 19.5±2.1, P=0.20). In Group B we found higher levels of NT-proBNP (2105±1015 pg/mL vs. 915±320 pg/mL in Group A, P=0.04). After G-CSF stimulation, we found significantly lower numbers of EPCs in Group A (62±48 x10
6
cells/L) than in Group B (98±54 x10
6
cells/L, P=0.01). Similarly, apheresis yielded lower numbers of EPCs in Group A (82±72 x10
6
cells vs. 187±90 x10
6
cells in Group B, P=0.01). When compared to Group B, patients in Group A had lower levels of pro-angiogenic biomarkers (agiopoietin-1: 6.8±2.3 ng/mL vs. 12.1±4.9 ng/mL, P=0.01; vascular endothelial growth factor: 22.5±18.2 pg/mL vs. 53.2±19.1 pg/mL, P=0.01), and higher levels of anti-angiogenic biomarkers (endostatin: 61.3±17.4 ng/mL vs. 31.7±12.2 ng/mL, P=0.01; thrombospondin-2: 17.1±3.9 ng/mL vs. 9.0±4.5 ng/mL, P=0.02).

Conclusion:
In patients with HFpEF, obesity appears to be associated with reduced mobilisation of endothelial progenitor cells and impaired angiogenesis.
Abstract 4141147: Age at Menarche Associated with Longitudinal Increases in Blood Pressure in Postmenopausal Indian Women: Data from the Centre for Cardiometabolic Risk Reduction in South-Asia (CARRS) study
Authors: Quarpong Wilhemina , Chandrasekaran Suchitra , Mehta Puja , Narayan K , Tandon Nikhil , Ramakrishnan Usha , Patel Shivani
Published: November 2024

Background and research questions:
Data suggest that South Asian women exhibit earlier development of cardiovascular disease and that they may also experience menarche and menopause at younger ages than other ethnic groups. We investigated whether the timing of menarche and menopause impacts the trajectories of blood pressure in postmenopausal women in India.

Methods:
Data were from 1,689 postmenopausal women free of cardiovascular disease at baseline in the Delhi and Chennai sites of the Centre for cArdiometabolic Risk Reduction in South-Asia (CARRS) surveillance Cohort. Women underwent blood pressure examinations at their homes in 2010-2012, 2013-2014, and 2016-2017. We assessed associations of ages at menarche (tertiles: 9-13, 14, and 15-22 years) and menopause (four categories: <40, 40-44, 45-49, and ≥50 years), separately, with baseline systolic blood pressure (SBP) and trajectories of SBP change from baseline to the last available examination round. Associations were assessed using multilevel modeling, controlling for age, education, employment status, religion, body mass index, and hypertension diagnosis and/or use of antihypertensive medication at baseline.

Results:
Women had a median age of 54 years (IQR: 48-60) at baseline and median follow-up time was 4.8 years (IQR: 4.1-5.2). Median age at menarche was 14 years (IQR: 13-15) and median age at menopause was 45 years (IQR: 40-48). Adjusted models showed no association between age at menarche and baseline SBP. Longitudinally, the percent change in SBP per year was higher for those who had menarche before age 14 (0.83, 95% CI: 0.53-1.14) and after age 14 (0.70, 95% CI: 0.38-1.04) compared to menarche at 14 years (0.25, 95% CI: -0.06-0.55). There were no statistically significant associations of age at menopause with baseline SBP or change in SBP.

Conclusions:
The timing of menarche, but not menopause, was associated with blood pressure trajectories among postmenopausal Indian women. Further work to understand the mechanisms linking reproductive milestones and blood pressure trajectories as well as their implications for cardiovascular outcomes in South Asian women is needed.
Abstract 4141154: The role and molecular mechanisms of cold-inducible RNA-binding protein in neural injury after acute ischemic stroke
Authors: Shao Kangmei
Published: November 2024

Background:
Acute ischemic stroke (AIS) is one of the leading causes of death and disability in adults worldwide, and effective treatments are still lacking. Cold-inducible RNA-binding protein (CIRP) is up-regulated in response to various stress conditions. Previous studies have indicated that CIBP could potentially influence the development of various diseases.

Research questions:
Nevertheless, the specific role and molecular mechanism of CIBP after AIS remain unclear.

Methods:
The levels of serum CIRP and other brain injury markers such as NSE, S100β, GSDMD, and NLRP3 were measured by ELISA to explore the relationship between CIRP and AIS. Additionally, middle cerebral artery occlusion models (MCAO) in rats were established to investigate its localization in brain tissue using immunofluorescence staining. Additionally, the CIRP knockout MCAO rat model was established, and evaluate the effect of CIRP deficiency on the neurological function of rats. while the role of CIRP was investigated through RNA sequencing and Western Blot analysis. Additionally, the potential protective effect of the CIRP inhibitor C23 on neural injury following AIS was examined.

Results:
(1) Compared to the healthy control group, the serum levels of CIRP and other brain injury markers (NSE, S100β) in AIS patients and MCAO rats were significantly elevated, and the elevated levels were positively correlated. (2) In the MCAO rat model, the CIRP was mainly located in neurons and microglia. (3) Compared with wild-type MCAO rats, CIRP knockout MCAO rats improved neurological function scores. (4) RNA-seq analysis revealed that genes differentially expressed between wild-type MCAO rats and CIRP knockout MCAO rats were enriched in inflammation-related pathways. (5) The expression of pyroptosis-related proteins (NLRP3, Caspase-1, GSDMD, and ASC) and inflammatory factors (IL-1β, TNF-α, etc.) decreased in CIRP knockout MCAO rats. (6) The CIRP inhibitor C23 significantly alleviated brain injury and improved neurological function. C23 treatment significantly decreased the expression levels of pyroptosis-related proteins and inflammatory factors.

Conclusions:
This study shows that CIRP plays an important role in AIS development. The levels of CIRP in AIS patients and MCAO rats are significantly increased and are positively correlated with nerve damage markers. Thus, supporting CIRP as a potential target for the treatment of AIS. This discovery provides new strategies for the treatment of AIS.
Abstract 4141170: Impact of Serum 5-Hydroxytryptophan Levels on 15-Year Major Adverse Cardiovascular Events in ST-Elevation Myocardial Infarction Patients
Authors: Chia Chin-Yuan , Wang Chao-Yung
Published: November 2024

Background:
5-Hydroxytryptophan (5-HTP) is a natural amino acid and precursor to serotonin, which is essential for various physiological functions. In cardiovascular research, serotonin has been implicated in modulating vascular tone, platelet aggregation, and myocardial function. Another derivative of 5-HTP, 5-methoxytryptophan (5-MTP), has been associated with reduced inflammation and cardiovascular calcification. However, the specific cardiovascular effects of 5-HTP remain less understood. This study investigates the relationship between baseline 5-HTP levels and the incidence of major adverse cardiovascular events (MACE) in patients who have experienced ST-elevation myocardial infarction (STEMI).

Objective:
Our goal was to determine if higher 5-HTP levels at the time of initial blood draw correlate with a lower incidence of MACE during long-term follow-up.

Methods:
This prospective cohort study included 453 STEMI patients (mean age 69.8 years, 53 women) followed for up to 15 years. Baseline serum 5-HTP levels were measured, with 2.42nM used as the threshold to categorize patients into high and low 5-HTP groups. The primary outcome was the incidence of MACE, including death, acute myocardial infarction, recurrent angina, congestive heart failure, coronary artery bypass grafting, stroke, planned percutaneous coronary intervention (PCI), unplanned PCI, and atrial fibrillation.

Results:
During the 15-year follow-up, 232 patients (51.2%) experienced MACE. Using the Cox proportional hazards model, we found that patients with higher baseline 5-HTP level (≥2.42nM) had a significantly lower risk of experiencing MACE (hazard ratio: 0.747, 95% CI: 0.561-0.996). Further analysis using a multivariable Cox proportional hazards model, adjusting for hypertension (HTN), use of Clopidogrel, use of Ticagrelor, Killip class during the initial STEMI event, age, and gender, confirmed that high 5-HTP levels were independently associated with a lower risk of MACE (hazard ratio: 0.712, 95% CI: 0.510-0.995).

Conclusion:
Higher 5-HTP levels are independently associated with a reduced risk of MACE in patients after STEMI. These findings suggest that 5-HTP could potentially be used as a biomarker for cardiovascular risk stratification. Additionally, supplementation with 5-HTP might be explored as a therapeutic strategy to reduce the risk of subsequent MACE in this high-risk population. Further research is warranted to confirm these findings and to understand the underlying mechanisms.
Abstract 4141218: Prolonged Impella 5.5 Support – A Single-Center Experience
Authors: Kuznetsov Ivan , Kieserman Jake , Toubat Omar , Ranum Alison , Peterson Adrian , Brown Alyson , Biscotti Mauer , King Jacob , Cevasco Marisa , bermudez christian , Wald Joyce
Published: November 2024

Background:
The Impella 5.5 (Abiomed; I5.5) is a temporary mechanical circulatory support (tMCS) device currently approved for periods of ≤14 days. Although many centers have reported successful I5.5 utilization beyond this duration, the indications and clinical outcomes associated with this practice are unknown.

Methods:
We retrospectively analyzed patients at our institution receiving I5.5 from April 2021-September 2023. Inclusion criteria were patients which received I5.5 at our institution that reached first event– specified as death/hospice, durable VAD/heart transplant, or recovery – prior to discharge or transfer. The primary outcome was differences in first event between patients receiving I5.5 support for ≤14-days vs >14-days. Secondary outcomes were complication rates, defined by occurrence of bleeding, stroke, significant hemolysis, or device migration/malfunction. Propensity-matching was utilized to help account for potential confounders. Statistical analysis involved Wilcoxon rank-sum testing and Chi-square/Fisher’s exact tests with Benjamini-Hochberg correction.

Results:
Among the 162 patients which met inclusion criteria, 76 (47%) required ≤14-days of support and 86 (53%) required >14-days. Baseline demographics and baseline INTERMACS profile and SCAI class were similar. In the ≤14-days group vs >14-day group, 54% vs 72% progressed to durable VAD/transplant (p = 0.02), 28% vs 21% died/pursued hospice (p = 0.48), and 18% vs 7% recovered (p = 0.04). Sub-group analysis on a propensity-matched cohort with similar INTERMACS profile and SCAI classification did not alter the above results, with similar probability of death/hospice (p = 0.52) and increased probability of durable VAD/transplant (54% ≤14-days, 71% >14-days; p = 0.04). Time-adjusted complication rates between cohorts were similar (IRR = 1.1 ≤14 vs >14-days; 95% CI 0.3 - 1.9), but overall complication frequency was higher in the >14-day group (11% ≤14-days, 41% >14 days, p < 0.01).

Conclusion:
I5.5-based tMCS beyond 14 days was not associated with increased mortality or decreased probability of eventual durable VAD/transplant. We did not observe an increased incidence rate of complications for I5.5 usage beyond 14 days but did note an increased absolute probability of complications with prolonged support. Future randomized-control studies which better control for potential confounds are warranted to better identify appropriate indications for I5.5 tMCS utilization beyond 14 days.
Abstract 4141249: Circulating Follistatin-like 3 and its Association with Postpartum Cardiac Dysfunction and Severe Maternal Morbidity
Authors: Azzi Marly , Potchileev Sanela , Dreixler John , Mueller Ariel , Rana Sarosh , Shahul Sajid
Published: November 2024

Background:
Hypertensive disorders of pregnancy (HDP) is a leading cause of pregnancy-related mortality in the United States and an important risk factor for postpartum cardiovascular disease (CVD). Previous animal data suggested that FSTL3 expression may be pathogenic in the development of cardiovascular dysfunction. The incidence of CVD during pregnancy has been increasing over time, which highlights the need to identify biomarkers that affect the development of the disease. We therefore hypothesized that peripartum FSTL3 levels would be associated with postpartum cardiovascular dysfunction and maternal morbidity.

Methods:
Pregnant patients age ≥ 18 years and singleton < 41 weeks with preeclampsia or superimposed preeclampsia who delivered at the University of Chicago between May 2017 and November 2020 were included in this observational cohort study. The primary outcome was cardiovascular dysfunction defined as postpartum hypertension, cardiomyopathy (confirmed with echocardiography and cardiology consult), and pulmonary edema (confirmed with chest radiography). The secondary outcome was severe maternal morbidity. Categorical data were assessed with chi-square or Fisher’s Exact test. The association between FSTL3 levels and postpartum CV dysfunction was assessed using multivariable logistic regression.

Results:
Our study included 408 patients, of which 212 were diagnosed with HDP. The median age was 28 years old (IQR 23, 33), the median BMI was 33.4 (IQR 28.6, 39.3), and the majority were African American (67.1%). Elevated FSTL3 levels were associated with postpartum CV dysfunction (OR 1.02 [95% CI: 1.01, 1.04]; p < 0.001). After multivariable adjustment for delivery gestational age, maternal age, BMI, nulliparous, HDP, smoking, and diabetes, the association between FSTL3 and CVD persisted (p = 0.02). Table 1 outlines the association between FSTL3 and maternal/neonatal outcomes.

Conclusion:
This study demonstrates that the biomarker FSLT3 predicts postpartum cardiovascular dysfunction and is associated with maternal morbidity. Our findings suggest that FSLT3 may facilitate the development of CVD and that therapeutic strategies targeting FSLT3 may affect the course of postpartum cardiovascular dysfunction.
Abstract 4141299: Cannabis Use and Cardiovascular Crisis: A Meta-Analytical Evaluation of Stroke and Myocardial Infarction Risk
Authors: Agrawal Vibhor , Suresh Vinay , Dey Debankur , Raj Rishu , Kaur Anmol , Mohammad Adeeb Ali , Singh Priyansha
Published: November 2024

Background:
Cannabis is among the most widely used psychotropic substances globally. With its increasing prevalence, questions have arisen regarding its potential impact on cardiovascular and cerebrovascular health. While multiple studies have explored the association between cannabis use and the risk of cardiovascular and cerebrovascular diseases, findings across these studies have been inconsistent, necessitating a comprehensive evaluation to elucidate the true nature of this relationship.

Aim:
This meta-analysis aims to investigate the association between cannabis use and the risk of myocardial infarction (MI) and stroke.

Methods:
A systematic search was conducted in relevant electronic databases, including PubMed, EMBASE, and SCOPUS, from inception to April 2024. Inclusion criteria comprised observational studies evaluating the association between cannabis use and events such as MI and stroke. Two reviewers independently screened studies, extracted data, and assessed quality. A random-effects meta-analysis was performed to estimate pooled ORs and 95% CIs. Heterogeneity was assessed using I
2
statistic.

Results:
Our meta-analysis included data from 26 studies, with a total population of 72,551,926 individuals of whom 69.5% were female. Among these, 7,832,105 individuals (2.1%) were identified as cannabis users, with 41.2% being female. Cannabis users exhibited significantly higher odds of experiencing MI (OR= 1.38, 95%CI: 1.14-1.68) and stroke (OR= 1.43, 95%CI: 1.08-1.89) compared to non-users. When considering stroke subtypes, while the odds of ischemic stroke among cannabis users showed a trend toward elevation (OR= 1.60, 95%CI: 0.91-2.81), the difference was non-significant. Similarly, the odds of hemorrhagic stroke among cannabis users did not reach statistical significance when compared to non-users, (OR= 1.98, 95%CI: 0.80-4.88).

Conclusions:
Our analysis reveals a significant increase in the odds of both MI and stroke in cannabis users. Notably, we observed a comparable yet increased trend in both ischemic and hemorrhagic stroke subtypes. Further research is crucial to delineate these associations and understand the underlying mechanisms.
Abstract 4141389: Low Serum Albumin as a Predictor of All-Cause Mortality in HFpEF Patients
Authors: Lopuszynski Jack , Scott Christopher , Ahmad Rimsha , Zahid Maliha
Published: November 2024

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent form of heart failure (HF) in the US today. Our prior work revealed low albumin at first hospitalization for HF exacerbation with underlying HFpEF to be an independent predictor of all-cause mortality in a small cohort of patients. We now sought to confirm our earlier findings across a larger and more diverse patient population.

Methods:
Seven thousand, eight hundred and forty patients had a first admission to Mayo Clinic for HF exacerbation with an echo-confirmed left ventricular ejection fraction>50% between 2010 and 2020. Patient baseline demographics, co-morbidities, admission laboratory values, echocardiographic parameters, discharge medications, and outcomes were obtained from chart abstraction. To validate our previous model, patients were grouped based on the number of risk factors as previously defined: age>80 years, serum albumin level<3.2 g/dl, medial E/e'≥20, N-terminal pro-brain natriuretic peptide (NT-proBNP) >5,000 pg/mL, and the presence of hypertension (HTN). The association with 1 year mortality was studied using Cox regression. Kaplan Meier curves were generated based on the number of factors present per patient.

Results:
Eleven significant univariate predictors of all-cause mortality were identified from the data (Fig. 1A), with hazard ratios (HR) ranging from 1.22-2.04 (p<0.001 for all). Notably, four previously identified prognosticators (age, albumin, medial E/e’, , HTN) were noted as significant independent predictors of all-cause mortality in HFpEF (HR 1.67, 2.14, 1.18, and 1.15, respectively, p<0.004 for all ; Fig. 1B). Multivariate regression modeling identified low albumin on presentation as being a significant adverse prognosticator (HR=2.14; p-value<0.001).

Conclusion:
Our analysis of 7840 HFpEF patients confirms our prior findings, suggesting that this model is a strong predictive tool for assessing the prognosis of HFpEF. Taken together, these five variables are easily available in the in-patient setting and can be incorporated into a model predictive of 1-year all-cause mortality.
Abstract 4141396: Activation of the Wnt Signaling Pathway Links Atrial Myopathy to Atrial Fibrillation in Lamin A/C Heart Disease
Authors: Owais Asia , Chen Hanna , Chen Yining , Sridhar Arvind , Barney Miles , Baskaran Abhinaya , DeSantiago Jaime , Arif Mahmud , Darbar Dawood
Published: November 2024

Objective:
Pathogenic variants in
LMNA
are associated with early-onset atrial fibrillation (EOAF) but the pathophysiological mechanisms by which atrial myopathy leads to AF are poorly understood. Here, we investigated electrophysiologic (EP) and epigenetic mechanisms by which a heterozygous pathogenic
LMNA
-S143P mutation causes EOAF utilizing mature human induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCMs) generated from a large Caucasian kindred with a strong cardiac phenotype.

Hypothesis:
Atrial myopathy due to the
LMNA
-S143P mutation, creates an arrhythmogenic substrate for AF by causing ion channel and chromatin remodeling.

Approach:
We performed clinical phenotyping and genetic testing of the proband and family members. hiPSC-aCMs generated from family members and CRISPR-corrected isogenic control (CRISPR-GC) were characterized by optical voltage mapping, calcium transient measurements, and whole-cell patch clamp analysis. Transcriptomic and epigenetic analysis was performed by RNA-sequencing (seq) and assay for transposase-accessible chromatin followed by sequencing (ATAC-seq).

Results:
The proband presented with EOAF at 35 years. Cardiac MRI and transthoracic echocardiogram revealed an atrial myopathy and low voltage electrograms but preserved left ventricular ejection fraction (56%). Cascade screening of the
LMNA
-S143P kindred confirmed co-segregation of the variant with AF, conduction disease, and dilated cardiomyopathy
(Fig. A)
. EP analysis showed that the
LMNA
-S143P hiPSC-aCMs exhibited heterogeneity of action potential duration (APD)(
Fig. B
)
;
decreased Na
+
current
(Fig. C)
and delayed after-depolarizations
(Fig. D)
. Integrated analysis of RNA and ATAC-seq revealed significant enrichment of genes associated with Wnt signaling pathway, cytoskeletal remodeling and activation of calcium signaling (
Fig. E-I
) Congruently, we found high enrichment of CAMK2 kinase as well as TCF and NFAT transcription factors associated with Wnt signaling (
Fig. F-G
) .

Conclusion:
Our results suggest that cytoskeletal remodeling and triggered calcium release mediated by NFAT and CAMK2 respectively create an arrhythmogenic substrate for atrial myopathy and AF highlighting their therapeutic potential.
Abstract 4141409: Partnering With an American Indian Community to Co-Design a Structural Heart Disease Program to Improve Cardiac Care
Authors: Miller McCall , Vaughn Lisa , Benashley LeCario , Bones Billie , Buonfiglio Samantha , Lee-Gatewood Gwendena , Nashio JT , Paxson Amanda , Riley Alan , Rope Davalyn , Sarnacki Rachel , Walker Rhiannon , Whitesinger Dawnafe , Beaton Andrea , de Loizaga Sarah
Published: November 2024

Introduction:
American Indians are disproportionately impacted by cardiovascular disease. Furthermore, echocardiographic screening within one American Indian Tribe demonstrated ~6% of Tribal members had undiagnosed structural heart disease (SHD). Strategies for scale up of SHD screening are needed to improve earlier diagnosis and outcomes.

Aim:
Partner with the community to co-develop a scalable model to enhance SHD diagnosis, care, and outcomes that is culturally and contextually relevant for the partnering Tribe.

Methods:
We utilized a five-phase community-based participatory research approach outlined in Figure 1.

Results:
A five-member community research leadership board was established to bridge the gap between our research team and the community, in order to increase acceptability and program sustainability. Four group level assessment (GLA) sessions included 163 community members and identified the following five priorities as essential to a SHD program: 1) heart health/ SHD education and awareness; 2) cultural considerations; 3) inclusive, multigenerational community engagement; 4) improved resources for general health and wellness; and 5) accessible, patient-centered healthcare with local cardiac care. Follow-up semi-structured interviews were conducted with 19 community members. Thematic analysis identified key program needs including: 1) system considerations; 2) program considerations; 3) resources; 4) community awareness; 5) individual considerations/factors. Five personas were created based on emergent themes from the interviews: The Skeptic, The Hard-to-Reach, The Health Enthusiast, The Community Connector, and The Cultural/Tribal Champion. These personas were validated in community design workshops and used to identify barriers and facilitators of a SHD program, generate solutions to identified barriers, and prioritize program components based on impact and feasibility.

Conclusions:
We partnered with one Tribe to identify and co-develop the relevant and impactful components for an SHD program. Next steps include testing of programmatic implementation to understand reach, effectiveness, adoption, implementation, and maintenance.
Abstract 4141532: Time-Restricted Eating Improves Heart Rate, Symptoms, and Quality of Life Metrics in Patients With Postural Orthostatic Tachycardia Syndrome
Authors: Dzotsi Marissa , Strohm Allyssa , Manoogian Emily , Panda Satchidananda , Doherty Taylor , Taub Pam
Published: November 2024

Introduction/Hypothesis:
Time-restricted eating (TRE) is a lifestyle intervention in which there is an extended fasting period overnight of about 14 hours with a 10-hour eating window. Clinical and animal studies have shown that TRE decreases inflammation, and improves immune autonomic and mitochondrial function and cardiometabolic parameters. Patients with POTS have derangements in many of these parameters resulting in the hypothesis that TRE could be beneficial for patients with POTS.

Methods/Approach:
20 participants aged 18-70 (M=36 years ±11.79), all on pharmacological therapy for POTS, met inclusion criteria: ≥12-hour dietary window and established POTS diagnosis (≥30 bpm increase in upright heart rate). After a 2-week baseline period of monitoring via myCircadianClock App, to ensure baseline eating window was ≥12 hours, participants entered a 12-week TRE intervention, consuming calories within an 8-10 hour eating window. Pre/post-intervention assessments included a 10-minute stand test and QOL questionnaires (SF-36 and MALMO POTS).

Results/Data:
Orthostatic assessments comparing pre and post-intervention standing tests revealed reduction in heart rate increase. 19 of the 20 participants experienced this improvement, with the mean decrease in heart rate change (Figure 1A) averaging approximately 11 bpm (p < 0.001). Additionally, outcomes from the MALMO POTS Symptom Score Survey (MALMO) (Figure 1B) and the Short Form (36) Health Survey (SF-36) showcased substantial enhancements in participants' QOL. These improvements were evidenced by reductions in POTS symptom severity (p < 0.0001) and notable enhancements in physical functioning (p = 0.015) and energy/fatigue levels (p < 0.01).

Conclusion:
In this pilot study, TRE improved heart rate, symptoms and QOL in patients with POTS, who are on background medical therapy, suggesting this lifestyle intervention could be beneficial for patients with POTS.
Abstract 4141546: Acculturation Class Influences Physical Activity Among African Immigrants Living with Diabetes and/or Hypertension: A Qualitative Analysis
Authors: Osokpo Onome , Bracy Danny , Adeniji Dolapo O , Bankole Ayomide Okanlawon , Lewis Lisa , Riegel Barbara
Published: November 2024

Background:
Physical activity (PA) (e.g., walking) is critical for maintaining health, minimizing illness, and reducing mortality in adults living with diabetes and hypertension. Although acculturation may influence PA engagement, we know little about the PA of African immigrants who are more or less acculturated and factors perceived as barriers and facilitators to PA in this population.

Methods:
We conducted a descriptive qualitative study between March 2020 and September 2021 in the Northeastern U.S. We enrolled a purposive sample of 24 self-identified sub-Saharan African immigrant adults with symptomatic hypertension and/or diabetes. All spoke and understood English. Participants were classified as either high or low acculturated based on scores from a modified Short Acculturation Scale, reliability index (0.92), and validity index (0.65). Audio-recorded and transcribed interviews were imported to NVivo 13 and content analyzed to identify themes.

Results:
The sample was mean= 59 years (range 40-72). Most were Nigerian (n=16), male (n=16), married (n=17), living with family (n=21), highly educated (n=21), employed (n=16), and reported having enough to meet their needs (n=21). High acculturated participants were more (n=16). Both the high acculturated and low acculturated participants received information about PA from medical providers. Walking was the primary form of PA reported. Low acculturated participants walked with spouses/family members as is typically done back “home,” while high acculturated participants walked with friends/non-familial social connections, which is more Western. Although both groups used a treadmill or gym, only the high acculturated African immigrants had a gym membership. Family and friends facilitated PA; the high acculturated African immigrants were encouraged by friends to exercise, while the low acculturated stated that family motivated them to engage in PA. Arthritis, lack of enjoyment, mental stress, “laziness,” time, and neighborhood safety were barriers to engaging in PA.

Conclusion:
Interventions to promote PA should capitalize on socially relevant influences (e.g., family and friends) and address barriers to PA in immigrant populations.
Abstract 4141564: Disparities in Healthcare Utilization following Endovascular Abdominal Aneurysm Repair
Authors: St. John Emily , Marcaccio Christina , Ward Rebecca , Craig Robert , Gacchina Johnson Carmen , Torguson Rebecca , Fairman Ronald , Schermerhorn Marc , Secemsky Eric
Published: November 2024

Introduction:
Healthcare utilization in postoperative management and surveillance following endovascular aneurysm repair (EVAR) is an important factor in achieving long-term treatment success. However, factors associated with poor healthcare utilization have yet to be elucidated.

Hypothesis:
Disadvantaged patients have lower rates of surveillance and higher rates of emergency health service use than their counterparts.

Aims:
Examine rates of healthcare utilization stratified by age, sex, race, dual-enrollment in Medicare and Medicaid, and residence in a distressed community.

Methods:
We performed an observational retrospective cohort study of Medicare beneficiaries who underwent infrarenal EVAR with a bifurcated endograft between 2011-2019. We examined annual rates of post-operative surveillance (EVAR-related outpatient visits, surveillance imaging), use of emergency department (ED) visits, and hospital readmission across several disparity measures using Modified Poisson Regression models.

Results:
In 111,381 Medicare beneficiaries undergoing EVAR, comorbidities associated with poor postoperative surveillance were chronic kidney disease (aRR:1.06[1.04-1.07]), heart failure (1.10[1.09-1.11]), hyperlipidemia (1.16[1.14-1.19]), hypertension (1.09[1.07-1.12]), and ischemic heart disease (1.15[1.14-1.17]). For EVAR-related office visits, patients with worse post-operative care included those >85 years, female, Black, dual-enrolled, or living in distressed communities (
Table 1
). Similarly, less surveillance imaging was performed in patients >85 years, dual-enrolled, or living in distressed communities. There was a greater need for ER care or readmission among patients >85 years, female, Black, dual-enrolled, or living in distressed communities.

Conclusions:
Our study revealed patterns of disparities in post-procedure EVAR-related office visits and EVAR imaging studies, and greater use of emergency health services associated with patient age, sex, race, and socioeconomic status. These findings may suggest barriers in access to appropriate surveillance and care which could be addressed by targeting the identified groups for intervention efforts to improve EVAR surveillance.