bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4144773: Trends In Cerebrovascular Disease-related Mortality Among Older Adults In The United States From 1999 To 2020: An Analysis Of Gender, Race/Ethnicity, And Geographical Disparities.
Authors: Saad Muhammad , Saleem Maria , Maqbool Umar , Khan Fareeha , Saleem Maleeha , Alamgir Eman , Qazi Salvia , - Haram , Ali Aleena , Assad Arfa , Javed Aasma , Bin Abdul Ghaffar Qais , Adeel Ammad , Khan Faheemullah , Raja Adarsh
Published: November 2024

Background:
Cerebrovascular disease is a leading cause of morbidity and mortality in the US, mainly affecting older adults. Aging significantly influences its manifestations and pathophysiology, impacting late-life quality. However, mortality trends in cerebrovascular disease among older adults of different gender, race, and geographic areas have not been thoroughly examined. Understanding these correlations and current death patterns is crucial for improving medical treatment and strategies.

Research Aim:
To investigate the impact of gender, race, and geographic disparities on cerebrovascular disease-related mortality rates among older adults in the United States, utilizing CDC-WONDER data from 1999 to 2020.

Methodology:
Cerebrovascular disease-related data from the CDC-WONDER database (1999-2020) using ICD-10 codes I60-I69 were analyzed. Annual Percent Change (APC), and Age-adjusted mortality rates (AAMR) per 100,000 persons were calculated and stratified by gender, race, place of death, state, census regions, and urban/rural classification. Joinpoint regression was utilized to assess trend changes and APC.

Results:
Between 1999 and 2020, 3,813,729 elderly individuals died from cerebrovascular disease. Overall, AAMR decreased from 1264.3 to 812.5, yet a rise was noted from 2018 to 2020, particularly in males (APC 6.069* vs. 4.668* in females). Non-Hispanic (NH) Blacks showed the highest APC (8.026*) from 2018 to 2020, while NH American Indians or Alaska Natives declined from 2013 to 2020 (-0.926). Non-metropolitan areas consistently had higher AAMRs, sharply increasing since 2018 (APC 4.818* vs. 5.135*). The Midwest had the highest APC (7.253*) from 2018 to 2020, while the South had the lowest APC (4.598*). Tennessee had the highest overall AAMR (1076.3) from 1999 to 2020, and New York had the lowest AAMR (609.7). (Figure 1)

Conclusion:
Despite declining overall mortality, persistent disparities exist in cerebrovascular disease-related mortality, with NH black males and rural residents facing the highest rates. Urgent public health action is needed, given the alarming rise in mortality from 2018 to 2020.
Abstract 4144774: Machine Learning-Based Clinical Predictive Models for Early Readmission in Patients with Cardiogenic Shock
Authors: Tieliwaerdi Xiarepati , Abuduweili Abulikemu , Mutabi Erasmus , Manalo Kathryn , Lander Matthew
Published: November 2024

Background/Purpose:
Cardiogenic shock (CS) affects up to 50,000 people annually in the United States, with high in-hospital mortality rates of 40%-67%. About 18.6% of CS survivors are re-admitted. This study aims to predict 7-day and 30-day readmissions in CS patients using machine learning (ML) algorithms to guide targeted interventions and improve healthcare outcomes.

Methods:
This retrospective study used the 2019 National Readmissions Database (NRD). CS hospitalizations were identified using ICD-10 code R57.0. Welch’s t-test compared continuous variables. The dataset was split into training and testing sets with a 7:3 ratio. Commonly used ML models, including XGBoost, Adaboost, decision tree, and random forest, were compared with logistic regression (LR). The primary outcome was CS readmission within 7 or 30 days of discharge. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used for performance measurement.

Results:
Among 97,653 CS patients, 32,881 (33.7%) died during their initial hospitalization. Index hospitalizations were 51,976. We excluded hospitalizations where patients died during their initial stay, as these cases would not contribute to readmission data. Additionally, we only considered hospitalizations from January to November, excluding December hospitalizations since their 30-day readmissions would occur in the following year. The 7-day readmission rate was 4,317 (8.3%), and the 30-day readmission rate was 10,927 (21.02%). Significant predictors for both readmission periods (p value <0.05) included lower mean age, lower income, higher Medicaid coverage, lower private insurance coverage, higher rates of CKD3, chronic pulmonary disease, drug abuse, and diabetes with complications as shown in Table 1. Figure 1 shows the performance of various ML models, with XGBoost being the best model in both tasks, achieving an AUC of 0.65 for 7-day and 0.67 for 30-day readmissions, indicating less than a 70% chance of accurately predicting readmission. This performance was similar to that of LR (AUC of 0.61 and 0.67).

Conclusion:
ML models have poor capacity for early CR readmission prediction and perform similarly to logistic regression (LR) when developed using large administrative datasets. To enhance future model development, incorporating electronic health records (EHRs) with more detailed and clinically relevant data should be considered.
Abstract 4144803: Association of
ENTPD-1
SNP genotype on inflammatory cell phenotype and ST-elevation myocardial infarction cardiovascular outcomes: a post-hoc analysis of the POPular Genetics
Authors: van den Broek Wout , Watson Samuel , Bergmeijer Thomas , azzahhafi jaouad , Magorien Raymond , Mazzaferri Ernest , Lilly Scott , Attar Talal , Boudoulas Konstantinos , Madiai Francesca , Covarrubias Roman , ten berg jurrien , Gumina Richard
Published: November 2024

Background:
ST elevation myocardial infarction (STEMI) patients are at increased risk for secondary cardiovascular events. Modulation of purinergic signaling is the mainstay of post-MI antithrombotic therapy. CD39, encoded by the
ENTPD1
gene, is a key modulator of vascular homeostasis that hydrolyzes prothrombotic and proinflammatory extracellular nucleotides. The goal of this study was to determine if the
ENTPD1
promoter polymorphism rs3814159 genotype associates with inflammatory cell expression of CD39 and with secondary cardiovascular events in patients following STEMI.

Approach and Results:
FACS analysis of circulating inflammatory cells from volunteers and STEMI patients was conducted. We found that 1) the ENTPD1 promoter polymorphism rs3814159 genotype associates with the level of CD39 expression on T cells, 2) Integrated immunophenotype analysis depicts a temporal expression pattern of increased CD39 on Tregs following myocardial infarction, and 3) Treg phenotype differs by rs3814159 genotype early following STEMI. Next to determine if the rs3814159 genotype associates with STEMI outcomes we analyzed data from the POPular Genetics study. A total of 1964 patients from the original POPular Genetics study cohort had rs3814159 genotype assignment (

Treg CD39
high

AA: 517 (24.3%);

CD39
int

AG: 982 (46.2%);

CD39
low

GG: 625 (29.4%) consistent with expected frequencies. There were no differences in baseline characteristics by rs3814159 genotype. The primary endpoint of ischemic outcomes (all-cause death, myocardial infarction, target vessel revascularization, and/or stent thrombosis) was significantly higher in those patients homozygous for GG (

Treg CD39
low

) versus AA (

Treg CD39
high

) at rs3814159 by both univariate (HR:1.44; 95% CI:1.04-2.00, p=0.029) and multivariate (HR:1.43; 95% CI:1.03-1.98, p=0.034) analysis using an additive model. No significant differences in bleeding outcomes were observed by genotype using BARC criteria. Kaplan-Meier analysis revealed a significant increase in primary ischemic events in patient homozygous GG (

Treg CD39
low

) versus homozygous AA (

Treg CD39
high

) at rs3814159 (Figure).

Conclusions:
These data suggest for the first time that
ENTPD1
rs3814159 genotype associates with the level of CD39 expression on T-cells and with the incidence of the primary ischemic endpoint of all-cause death, myocardial infarction, target vessel revascularization, and/or stent thrombosis after ST elevation myocardial infarction.
Abstract 4144806: Epidemiology of Venous Thromboembolism and the use of Antithrombotic Strategies in Pediatric Patients with Congenital Heart Disease
Authors: Kiskaddon Amy , Do Nhue , Stock Arabela , Miles Alyssa , Ignjatovic Vera , Goldenberg Neil
Published: November 2024

Introduction:
Pediatric patients with congenital heart disease (CHD) are known to be at risk for venous thromboembolism (VTE). However, data describing the rate of recurrent VTE, types of cardiac surgery, and types/locations of index VTE are limited.

Aim:
The objectives of this study were to determine the rate of incident and recurrent VTE in pediatric patients with CHD undergoing cardiac surgery and evaluate the type of index surgery, index VTE location/site, and antithrombotic therapies.

Methods:
We queried the TriNetX Research database for patients under the age of 18 years from July 2016 to May 2024, who had a diagnosis of CHD and an index VTE. Descriptive statistics were employed.

Results:
Of 26,792 pediatric patients who underwent congenital cardiac surgery, 2225 (8.3%) developed an index VTE. Septal defect repair (n=574, 25.8%), shunt placement (n=502, 22.6%) and correction of single ventricle/complex cardiac anomaly (n=389, 17.5%) were the most common index cardiac surgeries in patients who developed index VTE. Lower extremity VTE (n=1219, 54.8%) was the most common type of index VTE. Unfractionated heparin (n=1441, 64.8%) was the most commonly utilized antithrombotic drug for index VTE treatment. Five hundred seventy-nine (26%) patients who underwent cardiac surgery developed at least 1 recurrent VTE within 1 year of the index VTE.

Conclusions:
Among pediatric patients with CHD that requires cardiac surgery, the rate of incident and recurrent VTE is higher than previously expected. Multicenter prospective cohort studies are warranted to further evaluate the rate of, and risk factors for, recurrent VTE, to facilitate future risk-stratified trials of antithrombotic therapy approaches in these children.
Abstract 4144811: Durability of Left Bundle Branch Area Capture over Time: A Single Center Retrospective Analysis
Authors: Jafry Ali , Noory Ali , Thosani Amit , Silverstein Joshua , Liu Emerson , Belden William , Chenarides John , Friehling Mati , Shaw George , Cherian Tharian
Published: November 2024

Background:
Left bundle branch area pacing (LBBAP) is a rapidly growing and widely adopted conduction system pacing (CSP) technique. However, little is known about the durability of left bundle branch area capture (LBBAC) over time.

Objective:
Evaluate durability of LBBA capture after achieving acute LBBAC at time of implant.

Methods:
Consecutive LBBAP implants or CSP upgrades by a single operator were retrospectively evaluated. A Medtronic (MDT) C315 sheath was used to deliver a MDT 3830 lead to the LBBA in all cases. QRS width, LV activation time (LVAT), V6-V1 inter-peak interval (V6-V1I) and the presence of R’ in V1 at the time of initial CSP implant and at most recent follow up ECG were measured to determine durability of LBBAC over time. LBBAC was defined as presence of R’ in V1, along with LVAT < 90 msec. Loss of LBBAC was defined as loss of R’ in V1 in follow up along with either increase in QRS duration and/or LVAT.

Results:
We attempted LBBAP in 108 pts with acute success in 92 (85.2%). The remaining 16 patients (14.8%) demonstrated deep septal pacing. Mean QRS duration at implant for those achieving acute LBBA capture was 130 +/- 12 msec, with mean LVAT of 72 +/- 12 msec, and V6-V1I of 46 +/- 18 msec. After excluding patients with minimal RV pacing and those lost to follow up, 46 patients with acute LBBAC had follow up ECGs available. After a median follow up of 300 days, 44 patients (96%) retained LBBAC with stable QRS duration (125 +/- 16 msec), LVAT (70 +/- 16 msec), and V6-V1I (43 +/- 19 msec). Two patients (4.3%) lost LBBAC, as evidenced by loss of R’, transition to an RV septal paced morphology, and increased LVAT and paced QRS duration. Pacing thresholds remained stable over time. No patients required upgrade for pacing induced cardiomyopathy.

Conclusion:
In this retrospective study, LBBAC is durable over approximately one year follow up. Longer term follow up data is required to determine long-term durability of this pacing technique, particularly in patients with CRT indications.
Abstract 4144814: A novel small molecule synthesized based on a snail hibernation model induces hibernation in mouse fibroblasts and perfused hearts
Authors: PIAO JIYUAN , Zhang Yongneng , Zhao Yuan Yuan , Hannington Patrick , Tabatabaei Dakhili Seyed Amirhossein , Ussher John , Sutendra Gopinath , Michelakis Evangelos
Published: November 2024

Animals during hibernation suffer no ischemic consequences from their very much decrease heart/respiration rates, otherwise incompatible with life, but humans lost the ability to hibernate (presumably when their ancestors gained independence from the weather) and are highly vulnerable to ischemia. In a snail hibernation model, we isolated a brain metabolite only present in the plasma and brain of hibernating snails, and we characterized it with HPLC/MS. We found it is an activator of PHLPP1, a critical phosphatase in the conserved AMPK/mTOR signaling networks implicated in hibernation and fuel sensing (O
2
, glucose, amino acids). We synthesized it chemically and named it Snail Neurometabolite Activator of PHLPP1 (SNAP). We hypothesized that SNAP may induce

hibernation in snails as well as mouse cells and organs that normally do not exhibit hibernation.

We utilized in vivo, in vitro and ex vivo models, using Alberta snails, mouse-derived fibroblasts and ischemia and reperfusion (IR) injury model with Langendorff-perfused mouse hearts, to assess the effects of SNAP on snail hibernation, as well as the fuel deprivation-induced stress resistance in mouse-derived cells and hearts.

SNAP injections in snails induced reversible hibernation indistinguishable from physiologic.

SNAP specifically dephosphorylates the PHLPP1 targets p-S6K and p-AKT (downstream of mTOR and AMPK respectively) in fibroblasts cultured in hypoxic and low-glucose conditions for 3 days, significantly suppressed O
2
consumption, apoptosis, and cell-cycle progression, but enhanced autophagy formation. Upon discontinuation of SNAP and return to normal culture conditions, the SNAP-treated cells had preserved metabolism and re-entered the cell cycle at much higher rates compared to the vehicle, suggesting protection from ischemia and reperfusion (IR) injury and entrance in a reversible hibernation-like state. Furthermore, SNAP conferred cardioprotective effects during IR injury by preserving LV pressure, max and min dp/dt and re-entering normal function much earlier at reperfusion compared to the vehicle.

SNAP offers protection from IR injury, inducing a hibernation-like state in mice cells and hearts, with wide implications for heart attack/stroke, preservation of donated organs for transplantation or even ultra-long space travel.
Abstract 4144822: Association between serum anion gap and short-term mortality in sepsis patients complicated by pulmonary hypertension: A cohort study based on MIMIC-IV database
Authors: Zhang Zeying , Liu Qiming
Published: November 2024

Background:
The relationship between anion gap (AG) and short-term mortality in intensive care unit (ICU) sepsis patients complicated by pulmonary hypertension (PH) remains unclear.

Methods:
Retrospective analysis of incident sepsis patients complicated by PH first admitted to ICU in MIMIC database (2008 to 2019) were enrolled. Short-term outcomes include in-hospital mortality and 28-day mortality. According to the AG value (17.0 mmol/L), patients were divided into high and low AG groups. The Kaplan-Meier survival curve was used to compare the cumulative survival rates of the high and low groups using the log-rank test. Multivariable Cox regression analyses were constructed to assess the relationship between AG and short-term outcomes in sepsis patients complicated by PH.

Results:
2012 sepsis patients with pulmonary hypertension were included. The in-hospital mortality rates (11.4%) and 28-day mortality rates (12.8%) in the high AG group were higher than those in the low AG group (5.0% or 7.2%, respectively;
P
< 0.001). The Kaplan-Meier curve showed that the in-hospital and 28-day cumulative survival rates were lower in the high AG group than that in the low AG group (
P
< 0.001). Multivariable Cox regression analysis confirmed that elevated AG was an independent risk factor of in-hospital mortality, 28-day mortality, length of stay in ICU and hospital. The relationship between elevated AG and in-hospital mortality remain stable after subgroups analyses.

Conclusions:
Elevated serum AG is associated with increased risk-adjusted short-term mortality in sepsis patients complicated by PH, and it may remind clinicians to identify patients with poor prognosis as early as possible.
Abstract 4144823: Persistent Prothrombotic State in Post-Acute Sequelae of Mild SARS-CoV-2 Infection: Role of Extracellular Histones and Immune Complexes
Authors: Patil Gokul , Ahmed Azaj , Miller Francis , Butler Noah , Comellas Alejandro , Garg Alpana , Dayal Sanjana
Published: November 2024

Post-Acute Sequelae of SARS-CoV-2 infection (PASC) have become a significant healthcare burden. Sustained increases in prothrombotic markers have been reported in hospitalized acute COVID-19 patients. However, whether patients with less severe acute infection also endure a persistent prothrombotic state remains uncertain. We tested for a prothrombotic state in this cohort and examined potential mediators. We enrolled 70 adult patients with prior mild acute SARS-CoV-2 infection and sustained PASC symptoms (per WHO criteria). A control healthy group matched for age and sex was also enrolled who were not previously diagnosed with COVID-19. Markers of platelet activation and platelet-neutrophil aggregates (PNA) were quantified using whole-blood flow cytometry. Markers of extracellular traps (citrullinated histones [H3Cit] and cell-free DNA [cfDNA]), anti-dsDNA IgG, and thrombin generation potential were measured in plasma. At recruitment (6 weeks to 3 years post infection), there was increased potential for thrombin generation in the plasma from PASC compared to control reflected by increased peak and velocity index (P<0.001 vs. control). In whole blood, activation with thrombin receptor activating peptide (TRAP) caused increased surface expression of P-selectin and activation of integrin αIIbβ3 in platelets (P<0.001 and P<0.05, respectively, vs. control). Concurrently, there was an increase in the PNA (P<0.01 vs. control). Plasma levels of H3Cit, cfDNA, as well as anti-dsDNA IgG were found to be elevated (P<0.0001 vs. control for all), suggesting not only an increase in extracellular trap, but also the existence of circulating immune complexes (ICs). While a histone-neutralizing aptamer inhibited P-selectin expression, αIIbβ3 activation, and PNA formation in whole blood, incubation of patient serum with anti-CD32, a FcγRIIa blocker (blocks the interaction of ICs with FcFcγRII on platelets), inhibited the activation of healthy platelets by patient sera. In conclusion, our study revealed a persistent prothrombotic state for months to years in patients who experienced mild acute infection with SARS-CoV-2. Further, our data suggest that the activation of platelet is partly mediated by extracellular histones and ICs, such as anti-dsDNA antibodies. Our findings suggest a model in which extracellular traps activate platelets directly and indirectly through ICs. This study proposes novel therapeutic interventions targeting extracellular histones and ICs-Fcγ in PASC.
Abstract 4144844: Comparison of Adjunctive Strategies Beyond Pulmonary Vein Isolation for Persistent Atrial Fibrillation: Cryoballoon-Based Left Atrial Modification vs. Posterior Left Atrial Box Isolation.
Authors: Yamashita Shuhei , Takatsuki Seiji , Himeno Yukihiro , yano shuhei , YAMAOKA KOKI , Ibe Susumu , Katsumata Yoshinori , Nishiyama Takahiko , KIMURA TAKEHIRO , Ieda Masaki
Published: November 2024

Background:
To improve outcome of catheter ablation for persistent atrial fibrillation (AF), adjunctive strategies targeting non-pulmonary vein triggers and atrial substrate modification were pursued.

Objectives:
To investigate the efficacy of cryoballoon left atrial roof ablation as an adjunctive ablation for persistent AF.

Methods:
This retrospective study included 448 consecutive patients who underwent their first ablation procedure for persistent atrial fibrillation at Keio University Hospital from January 2016 to May 2023. Using propensity score matching, we extracted 79 pairs who underwent cryoballoon left atrial roof ablation (CB-RA) or BOX posterior wall isolation (BOX-PWI) using radiofrequency. We evaluated procedural characteristics and the recurrence incidence of atrial arrhythmia after a 90-day blanking period within one year.

Results:
In the matched cohort of 158 patients (median age 64 [58-70], 88% male, 30.4% with longstanding persistent AF), 25 patients (15.8%) experienced atrial arrhythmia relapse after the blanking period within one year. CB-RA was successfully completed in 55 patients (69.6%), and touch-up radiofrequency roof line ablation was required in 24 patients (30.4%). Additional bottom linear ablation was performed with cryoballoon or radiofrequency in 22 patients (27.8%) in the CB-RA group, based on the physician’s decision during the procedure. Freedom from atrial arrhythmia recurrence was comparable between groups over one year of follow-up (83.5% for CB-RA vs. 84.8% for BOX-PWI; hazard ratio (HR) 1.34, 95% confidence interval (CI) 0.61–2.94, P=0.48).

Conclusion:
In Japanese clinical practice, cryoballoon-based left atrial modification as an adjunctive therapy for persistent atrial fibrillation demonstrated acceptable outcomes comparable to those of posterior left atrial box isolation using radiofrequency.
Abstract 4144880: GPR55 Promotes Mitochondrial Dysfunction and Atherosclerosis
Authors: Xu Keman , Saaoud Fatma , Lu Yifan , Shao Ying , Jiang Xiaohua , Hong Wang , Yang Xiaofeng
Published: November 2024

Introduction:
Atherosclerosis is the leading cause of death globally. Growing evidence suggests that mitochondrial dysfunction plays a significant role in atherosclerosis. However, the progression of mitochondrial energy generation disorders during atherosclerosis development remains unclear. In 2021, our lab indicated that activation of G-Protein Coupled Receptor 55 (GPR55) in human aortic endothelial cells (HAECs) could lead to EC activation, potentially increasing inflammation by altering mitochondrial transcription. EC activation is the central pathological event in atherosclerosis. However, whether and how mitochondrial dysfunction leads to EC activation
in vivo
and promotes atherosclerosis through the GPR55 pathway is still unknown.

Methods:
Lysophosphatidylinositol (lysoPI), an endogenous ligand for GPR55 activation, was used as a stimulus (20uM for 24hrs) to treat HAECs for Seahorse mitochondrial stress
in vitro
analysis. Wild-type mice, apolipoprotein E (ApoE-/-) deficiency mice, and GPR55/ApoE double knockout (DKO) mice were used for bulk RNA sequencing and
En face
analysis.

Results:
DKO mice showed a significant decrease in atherogenic lesions compared to ApoE-/- mice.
In vitro
Mito-stress indicated that GPR55 activation significantly increased basal respiration, spare capacity, maximal respiration, proton leak, and ATP production in HAECs, while inhibition of GPR55 reduced these parameters to basal levels. This suggests that GPR55 activation enhances mitochondrial function without affecting non-mitochondrial oxygen consumption, coupling efficiency, or mitochondrial membrane potential. We also generated a list of 289 genes associated with mitochondrial energy generation genetic disorders. Transcriptomic profiling of these genes in atherogenic mice fed with an HF diet for 3, 6, 12, 32, and 72 weeks showed a downward trend in significantly downregulated OXPHOS genes. This significant downregulation suggests increased OXPHOS biogenesis reprogramming as the disease progresses. Additionally, by comparing upregulated genes in ApoE-/- mice with those downregulated in DKO mice, we identified seven potential genes downstream of GPR55 signaling, including M2, MP, A1, F4, P8, H10, and S2, which are involved in the TCA cycle and metabolism, protein import, and lipid modification.

Conclusion:
Our study provides the first comprehensive examination of how impairments in mitochondrial OXPHOS biogenesis influence atherosclerosis progression via GPR55 signaling.
Abstract 4144884: Optimizing Large Language Models for Interpreting American Heart Association Dietary Guidelines in Nutrition Education for Cardiovascular Disease Prevention: A Retrieval-Augmented Generation Framework
Authors: Parameswaran Vijaya , Bernard Jenna , Bernard Alec , Deo Neil , Bates David , Lyytinen Kalle , Dash Rajesh
Published: November 2024

Introduction:
Large language models (LLMs) show proficiency in clinical capabilities such as responding to medical inquiries, and summarizing information, but their application in patient education requires evaluation. This study optimizes LLMs' interpretation of dietary guidelines for nutrition education using a framework that integrates American Heart Association (AHA) guidelines with Retrieval Augmented Generation (RAG), outperforming the baseline models.

Methods:
Analyzing 105 dietitian-authored visit notes (623,214 words) with Latent Dirichlet Allocation revealed two themes (coherence score 0.9). We posed 30 questions on these themes, along with the prompt, “Answer the following question as if you were a dietitian and cite sources from AHA,” three times to the baseline Perplexity (perplexity.ai), GPT-4o (OpenAI) models, and a customized LLM framework using RAG with formatted guidelines and citations applied to the Llama 3 70B model (Meta). Three expert reviewers evaluated the responses, scoring 0 or 1 for reliability, appropriateness, guideline adherence, and harm (Figure 1). Mean scores across groups were compared using analysis of variance.

Results:
Our LLM framework scored higher than baseline Perplexity and GPT-4o models on reliability (0.57±0.45 vs. 0.24±0.42, 0.11±0.25; p<.001, 95% CI [.07, .25]), appropriateness (0.83±0.28 vs. 0.62±0.34, 0.57±0.37; p<.001, 95% CI [.06, .23]), guideline adherence (100% vs. 47.5%, 80%; p<.001, 95% CI [.21, .41]), readability using the Flesch-Kincaid grade level (11.1±2.4 vs. 9±2.1, 9.4±1.8; p<.001, 95% CI [.07, .25]), and showed no harm (0 vs. 0.23±0.43, 0.26±0.44; p<.001, 95% CI [.02, .17]). Cohen’s kappa coefficient (k>70%, p<.001) indicates high reviewer agreement.

Conclusion:
The baseline models scored lower across all measures and included Type 2 errors. While the optimized model shows promise, improvements in reliability, readability, and inclusivity of dietary restrictions, preferences, and cultural considerations are needed for ethical and equitable clinical use. Future steps include refining model capabilities, building a comprehensive knowledge base, and field testing to assess impact of these improvements on clinicians' educational and documentation tasks.
Abstract 4144892: Thymidine phosphorylase plays a mechanistic role in lipid metabolism and obesity
Authors: Jividen Robbie , Yue Hong , Li Wei
Published: November 2024

Background:
Obesity is an independent risk factor for the development of type II diabetes (T2DM), metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiovascular disease (CVD). Imbalanced lipid metabolism and chronic inflammation are the major contributing factors for the development of obesity and T2DM, and their associated MASLD and CVD. Thymidine phosphorylase (TYMP) plays an important role in platelet activation and thrombosis in response to vascular injury, including in obese and diabetic mice. Scattered studies suggest that TYMP is increased in obese individuals and is present in the lipid-rich core of human atherosclerotic lesions.

Hypothesis:
TYMP is essential for lipid metabolism and the development of obesity.

Methods:
WT and male

Tymp
–/–

mice were fed a Western diet (WD), starting from 8 weeks of age, and food intake and body weight gain were monitored for 8 weeks. Liver and perigonadal fat tissue weights and the small intestine length were measured upon sacrifice. Fecal density was measured by the time taken to sink into water. TYMP and CD36 expressions in the small intestine of mice fed a chow diet or the WD were measured by qPCR and immunostaining.

Results:
TYMP deficiency dramatically reduced the gain of body weight, liver, and visceral fat weight in male, but not female, mice (
Figure 1
). The length of the small intestine was significantly longer in male

Tymp
–/–

mice compared to WT mice, but similar in females (
Figure 2
). Male

Tymp
–/–

mice showed an increased sensitivity to insulin (
Figure 3
). The liver exhibited the highest TYMP expression in mice, followed by the lungs and small intestine. Fecal density was lower in male

Tymp
–/–

mice consuming the WD, but there was no difference in mice consuming a normal laboratory diet. These data suggest that the feces of male

Tymp
–/–

mice may contain more fat. WD feeding increased the expression of TYMP and CD36 in the small intestine, while CD36 expression was dramatically reduced in

Tymp
–/–

mice. TYMP deficiency also attenuated CD36 expression in the liver of WD-fed mice.

Conclusion:
Our data suggest that TYMP plays a key role in regulating lipid metabolism, likely by upregulating intestinal CD36 expression, thus leading to increased lipid absorption and the development of obesity. Targeted TYMP inhibition may be a novel anti-obesity therapy.
Abstract 4144907: Left ventricular-arterial coupling and mortality in the cardiac intensive care unit
Authors: Padkins Mitchell , Fazzini Luca , Berg Kristoffer , GORI MAURO , Oh Jae , Kane Garvan , Hillerson Dustin , Tavazzi Guido , Jentzer Jacob
Published: November 2024

Background:
Ventricular-arterial coupling (VAC) refers to the ratio of afterload (effective arterial elastance) to contractility (left ventricular (LV) end-systolic elastance) as an integrated marker of cardiac performance. Echocardiography might be used to evaluate VAC through a simple time-efficient bedside evaluation.

Hypothesis:
VAC is useful for mortality risk stratification in an unselected cardiac intensive care unit (CICU) cohort.

Aims:
We sought to determine whether the VAC ratio, defined using the ratio of LV end-systolic volume (LVESV) to stroke volume (SV), predicted mortality in the CICU.

Methods:
Consecutive patients admitted to the Mayo Clinic CICU between 2007 and 2018 were included. The simplified VAC ratio was calculated as the LVESV calculated from 2D measurements using the Teichholz formula divided by the SV calculated from the LV outflow tract pulsed wave Doppler measurement, with values >1 reflecting ventricular-arterial uncoupling. The main outcome was all-cause in-hospital mortality.

Results:
We included 4685 patients with a median age of 69 (58-79) years; 37% were females. The median VAC ratio was 1.0 (0.7 to 1.8) and 21% of patients had a VAC ratio >2. Most clinical and echocardiographic variables differed in patients with higher VAC ratio, reflecting greater severity of illness with worse cardiac systolic and diastolic function. A total of 329 (7.0%) patients died during hospitalization. An incremental association was observed between a higher VAC and in-hospital mortality (unadjusted OR 1.22, 95% CI 1.16-1.29, p<0.001). Patients with a VAC ratio >1 (unadjusted OR 2.85, 95% CI 2.22-3.69, p <0.001) and especially those with VAC ratio >2 (unadjusted OR 4.28, 95% CI 3.24-5.69, p<0.001) had higher in-hospital mortality overall and in each admission diagnosis subgroup of interest (
Figure
). After multivariable adjustment, patients with a VAC ratio >2 remained at higher risk of in-hospital mortality (adjusted OR 1.63, 95% CI 1.17-2.28, p = 0.01).

Conclusions:
Ventricular-arterial uncoupling was associated with worse outcomes in an unselected CICU cohort. The echocardiographic VAC ratio is a simple non-invasive bedside measure that can be used for risk prediction in the CICU.
Abstract 4144918: Association of iron deficiency correction with the improvement of left ventricular systolic function in patients within 12 months after myocardial infarction
Authors: Khastieva Dilyara , Tarasova Natalia , Khasanov Niiaz
Published: November 2024

Background:
The adverse effects of iron deficiency (ID) on left ventricular function and outcomes in patients with acute coronary syndrome have been established. However, the effects of ID and its treatment in patients with myocardial infarction (MI) have not been adequately studied.

Aim:
To study left ventricular systolic function, assessed by evaluation of the wall motion score index (WMSI) and left ventricular ejection fraction (LVEF), in patients with corrected ID and persistent ID within 12 months after MI.

Methods:
This is open prospective study. 100 patients, 53 males (53%), and 47 females (47%) hospitalized with MI in "Kazan city clinical hospital 7" were enrolled in 2022 year. The mean age was 62±13 years. All patients had ID. ID is assumed to be present when serum ferritin <100 ng/mL or 100 ng/mL ≤ serum ferritin ≤299 ng/mL with transferrin saturation<20%. All patients were treated with iron supplements. After 3 months iron status was evaluated again, and the patients were divided into 2 groups: Group 1 - 70 (70%) patients with corrected ID and group 2 - 30 (30%) patients with persistent ID after the treatment. Echocardiography is performed within 24 hours and 3, 6, 12 months after MI.

Results:
The groups did not differ in major clinical parameters, comorbidities, medications, laboratory parameters, including hemoglobin level. The median (Me) of WMSI in the 24 hours after admission was 1.25 [1.19;1.62] in group 1 and 1.25 [1.12;1.56] in group 2 (p=0.55). In group 1, the Me WMSI at 3 months remained unchanged (1.25 [1.19;1.5], p =0,5), and was significantly lower than baseline at 6 months (1.19 [1.06-1.56], p < 0.001) and at 12 months (1.12 [1.0;1.44], p < 0.001). In patients in group 2, the Me WMSI remained unchanged at 3 months (1.25 [1.03;1.5], p=0.5), 6 months (1.25 [1.03;1.5], p=0.8) and 12 months (1.25 [1.0;1.5], p=0.6)(Pic. 1). The Me LVEF in the 24 hours after admission was 48% [45;54] in group 1 and 53% [48;54] in group 2 (p=0.06). In group 1, the Me LVEF remained unchanged at 3 months (48% [46;54], p=0.25) and was significantly increased than baseline after 6 months (53% [45;58], p<0,001) and 12 months (55% [47;58], p<0,001). In group 2, LVEF remained unchanged at 3 months (53% [46;57], p=0.75), at 6 months (53% [47;57], p=0.2) and 12 months (53% [46;58], p=0.7).

Conclusion:
Corrected ID is associated with a significant improvement of left ventricular systolic function in comparison with persistent ID in patients within 12 months after MI.
Abstract 4144996: General Capillary Endothelial Cells Undergo Reprogramming into Arterial Endothelial Cells in Pulmonary Hypertension
Authors: Liu Bin , Yi Dan , Xia Xiaomei , Ramirez Karina , Zhao Hanqiu , Tripathi Ankit , Fallon Michael , Dai Zhiyu
Published: November 2024

Introduction:
Pulmonary arterial hypertension (PAH) is characterized by a progressive increase of pulmonary vascular resistance and obliterative pulmonary vascular remodeling that result in right heart hypertrophy, failure, and premature death. The underlying mechanisms of loss of distal capillary endothelial cells (ECs) and obliterative vascular lesion formation remain unclear.

Method and Results:
Our recent single-cell RNA sequencing, spatial transcriptomics analysis, RNASCOPE, and immunostaining analysis showed that arterial ECs accumulation and loss of capillary ECs were evident in human PAH patients and pulmonary hypertension (PH) rodents. Pseudotime trajectory analysis of the single-cell RNA sequencing data suggests that lung capillary ECs transit to arterial ECs during the development of PH. Our study also identified CXCL12 as the marker for distal arterial ECs in PH. General capillary EC lineage tracing approach using Plvap-DreERT2; Tdtomato mice demonstrated that general capillary ECs gave rise to arterial ECs during PH development. Genetic deletion of HIF-2a or Notch4 neutralized antibodies normalized the arterial programming in PH.

Conclusion:
In conclusion, our study demonstrates that general capillary endothelium transits to arterial endothelium through the HIF-2a-Notch4 pathway during the development of PAH. Thus, targeting arterial EC transition might be a novel approach for treating PAH patients.

Acknowledgment:
This work was supported in part by NIH grants R00HL138278, R01HL158596, R01HL62794, R01HL169509, R01HL170096, AHA Career Development Award 20CDA35310084, The Cardiovascular Research and Education Foundation, Arizona Biomedical Research Centre funding (RFGA2022-01-06), and University of Arizona institution funding to Z.D.
Abstract 4144997: Pro-B-Type Natriuretic Peptide Kinetics across Pre-, Index, and Post-Acute COVID-19 in Hospitalized Acute on Chronic Heart Failure Patients: A Learning Health System Science Initiative
Authors: Wojtas Caroline , Vargas Ian , Taylor Robert , Rosario Manuel , Khurana Aman , Hamad Karen , heibel richard
Published: November 2024

Introduction:
Myocardial injury in patients hospitalized with acute on chronic heart failure concurrent with index SARS-CoV-2 (CoV-2) infection is well described, though studies incorporating pre- and post-acute COVID-19 (PAC) are lacking. We address this gap by estimating intensity of acutely decompensated heart failure (ADHF) using time-series pro-BNP levels across hospitalizations pre- vs. respectively index and initial readmission (PAC1).

Hypothesis:
Case time series analysis will reveal association (p<0.05) between changes in baseline (<24h of admission) pro-BNP levels at pre-index (<180d) vs. respectively index and PAC1 (<90d) with hospital length of stay (LOS) / Medicare Severity Diagnosis Related Groups Geometric Length of Stay (GMLOS) ratio (LOS/GMLOS) >1.0.

Methods:
Electronic health records underwent IRB exempted extraction of administrative, demographic, and clinical-pathophysiologic data. Continuous data summarized with median [IQR] were compared using repeated-measures ANOVA and discrete data with chi-squared testing. Confounders were statistically balanced.

Results:
Among 1,413 patients hospitalized between March 10, 2020 and February 29, 2024 discharged alive, not to hospice, harboring ADHF and CoV-2 infection, 91 respectively had baseline pro-BNP at Index and a pre-index hospitalization. Twenty-two underwent PAC1. Statistically isomorphic age, sex and race included 76 (68, 84) years, 43% females distributed by White (83%), Black (11%) and other races (6%). Similarly,chronic comorbidities were pooled for summary including hypertension (87%), chronic lung disease (46%), diabetes (41%), renal disease (36%), obesity (35%), and deficiency anemia (35%). Median times pre-DC to index hospitalization (56 [23, 114]) vs. Pre-DC to PAC1 admission (37 [15, 45]) days (p<0.001). Median pro-BNP (pg/mL) at Pre- (1948 [903, 4309]), Index (3081 [1458, 7230]), and PAC1 (2505 [ 1628, 8048]). Threshold increase in baseline pro-BNP associated with increased risk of LOS/GMLOS >1.0 between pre-COVID-19 vs. index and PAC1 respectively was >20% (p=0.013) and >14% (p=0.039).

Conclusions:
Time series pro-BNP levels obtained at serial hospitalizations can identity ADHF patients likely to exceed MS DRG GMLOS. Moreover, self-matched designs may strengthen patient-oriented learning health system science aiming to understand causal relationships between exposures and identify treatable traits to blunt or obviate duration of ADHF requiring hospitalization.
Abstract 4145048: PAROXYSMAL ATRIAL FIBRILLATION PATIENTS ON ANTICOAGULATION PRESENTING WITH EMBOLIC STROKE: A NATIONWIDE ANALYSIS
Authors: Joseph Varughese Vivek , Anil Peethambar Gowri , JAYARAJ RANJINI NIVED , Mummadisetty Anvitha , Sen Souvik
Published: November 2024

Introduction/ Background:
Paroxysmal Atrial Fibrillation is a clinical condition that increases the risk for embolic stroke. Current guidelines suggest anticoagulating patients with atrial fibrillation when the chadvasc score is > 2 to decrease the risk of embolic stroke.

Aim/ Research Questions:
Analyze comorbid conditions that holds significant associations with occurence of embolic stroke in paroxsymal atrial fibrillation admissions while being on long term anticoagulation.

Methods/Approach:
We used National inpatient Sample (2019) to identify admissions for embolic pattern stroke, with documented history of Paroxysmal Atrial Fibrillation (p AFib) on chronic anticoagulation (AC) (Age group > 18 years).Prevalence of comorbid conditions in the cohort was analyzed. Associations of the comorbid conditions with occurrence of embolic stroke in the admission cohort was analyzed using multivariate linear regression. A two tailed p value < 0.05 was used to define significance in all the calculations.

Results/Data:
(descriptive and inferential statistics) Of 4780 admissions for embolic stroke with comorbid Pafib on chronic AC were identified. Mean age of the admission cohort was 76.94. Of the admissions, 38.192% had congestive heart failure, 25.83% had chronic kidney disease, 41.94% had uncontrolled hypertension, 54.18% had diagnosis of unspecified hyperlipidemia, 0.523% had Hypertrophic obstructive cardiomyopathy, 0.73% had rheumatic/non rheumatic mitral stenosis listed as their comorbidities. Statistically significant association was seen between uncontrolled hypertension and occurence of embolic stroke OR: 1.997. 95%: 1.756- 2.27. Documented diagnosis of unspecified hyperlipidemia had statistically significant association with admissions for embolic stroke in the patient cohort: OR: 1.642, 95% CI: 1.214 – 1.845). Presence of coexisting HOCM and Mitral stenosis had positive ODDs but did not reach statistical significance {HOCM: OR :1.50, 95% :0.062 - 3.63 and Mitral stenosis: OR: 1.59, 95%: 0.075- 3.36). (Table 1) There was no statistically significant association between CHF, CKD, smoking or with presence of prosthetic valve with embolic stroke.

(HOCM: hypertrophic obstructive cardiomyopathy) (OR: Odds Ratio)

Conclusion(s):
Based on our analysis, presence of uncontrolled hypertension and hyperlipidemia had significant association with the occurrence of embolic stroke in paroxysmal atrial fibrillation population who were on long term anticoagulation.
Abstract 4145052: Impact of Postprocedural Delirium on Inpatient Outcomes in Transcatheter Aortic Valve Replacement Patients: A Retrospective Propensity Matched Analysis
Authors: Haseeb Shahan , Qureshi Muhammad Ahmad , Ahmed Omair , Munir Shafia , Siddiqui Taha , Gehres Eric , Zaman Muhammad , Ali Raiyan , Dwivedi Manu , Ansari Umair , Zulqarnain Muhammad
Published: November 2024

Introduction:
Transcatheter Aortic Valve Replacement (TAVR) is an increasingly common procedure for patients with severe aortic stenosis. However, postprocedural delirium remains a significant complication, impacting patient outcomes. This study aims to evaluate the inpatient outcomes of delirium in patients undergoing TAVR.

Methods:
We performed a retrospective cohort study using the National Inpatient Sample 2018-2020, including patients who underwent TAVR with and without delirium. Propensity score matching was performed using the variables age, elective admission, sex, and comorbid conditions (congestive heart failure, cardiac arrhythmias, peripheral vascular disorders, hypertension, diabetes, chronic kidney disease, coagulopathy, and obesity) to compare patients with and without delirium. Weighted samples were utilized and p value <0.05 was considered significant.

Results:
Out of 205,565 TAVR patients, 1,995 (0.97%) experienced delirium. Delirium was associated with older age (median age 83 vs. 80 years, p<0.05), higher prevalence of congestive heart failure, cardiac arrhythmias, valvular disease, and coagulopathy. Patients with delirium had significantly longer median LOS (7 (3-15) vs. 2 (1-3) days, p<0.05). Delirium was a significant predictor of in-hospital mortality (OR 4.08, 95% CI 2.55-6.52, p<0.05) and MACE (OR 1.72, 95% CI 1.34-2.21, p<0.05). After propensity score matching, delirium remained associated with increased median LOS (7 (3-14) vs. 2 (1-6) days, p<0.05); however, the difference in mortality (3.9% vs. 1.7%, p=0.07), and MACE (20.4% vs. 15.2%, p=0.06) became statistically insignificant after propensity matching. Detailed results are mentioned in Table 1.

Discussion:
Our study highlights that delirium in TAVR patients is associated with significant adverse outcomes, including prolonged hospitalization, higher mortality and MACE rates compared to patients without delirium. The findings underscore the importance of identifying high-risk patients preoperatively and implementing strategies to mitigate delirium, thereby improving patient outcomes. Future research should focus on developing targeted interventions to prevent delirium in this vulnerable population.
Abstract 4145104: Can Stress Echocardiography during Cardiopulmonary Exercise Testing Help Predict Clinical Outcomes in Right-Sided Congenital Heart Disease?
Authors: Dizon Samantha , Krishnamurthy Yamini , Kochav Jonathan , Lewis Matthew , Rosenbaum Marlon , zemer wassercug noa
Published: November 2024

Background:
The optimal timing for intervention for pulmonary and right ventricular outflow tract stenosis in adult congenital heart disease (ACHD) remains uncertain. While stress echocardiography is an established modality to improve risk stratification in stenotic left-sided lesions, its utility in right-sided valve disease in the ACHD population has not been studied. We assessed if stress echocardiographic assessment of right ventricular (RV) function during cardiopulmonary exercise testing (CPET) can facilitate risk stratification in the ACHD population.

Objectives:
The purpose of this study was to determine the relationship between RV augmentation on stress echocardiogram during CPET and morbidity in ACHD patients with sub-pulmonary right ventricles and right-sided stenotic lesions.

Methods:
A retrospective cohort study of ACHD patients with sub-pulmonary right ventricles who underwent CPET with stress echocardiogram was performed. The primary outcome was defined as having at least one of the following: 1) cardiac related hospitalization, 2) new documented arrhythmia, or 3) new or worsening heart failure. RV augmentation on stress echo was verified by concordance with a second observer.

Results:
The study included 87 patients, 41 (47%) with repaired tetralogy of Fallot, 9 (10.3%) with RV-PA conduits, and 9 (10.3%) with pulmonary stenosis. On baseline transthoracic echocardiogram, median peak pulmonary valve gradient was 38.7 mmHg (Q1 17.9 , Q3 49.0) and 30% of patients had RV dysfunction. On stress imaging, 13 (14.9%) did not demonstrate RV augmentation. Those without RV augmentation had a lower percent predicted peak Vo2 (61.4% vs 75.4%, p=0.007). Eleven (12.6%) met the primary outcome. Lack of RV augmentation was strongly associated with the primary outcome (OR 4.25, CI 1.04 –17.46, p = 0.04). This association remained true in patients with baseline peak PV gradients less than 50mmHg (OR 8.7, CI 1.68 – 46.79, p = 0.009) and was more pronounced in patients with tetralogy of Fallot (OR 33.99, CI 3.29 – 829, p = 0.007).

Conclusions:
Lack of RV augmentation on stress echo during CPET is associated with increased morbidity in ACHD patients with right-sided stenotic lesions. These results suggest that stress echocardiography at the time of CPET should be considered in this population.