bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14341: Older Patients Do Well Following Surgical Treatment of Infective Endocarditis
Authors: Boettger Priyanka , Buerke Michael
Published: April 2024

Introduction:
Evidence for the role of surgery in the management of infectious endocarditis (I.E.) is conflicting and there is no data relating specifically to the elderly subgroup. We hypothesised that for I.E., the elderly have different presentation, treatment profile and outcomes compared to the remainder of the adult population.

Methods:
We collected registry data on consecutive cases of IE treated in our tertiary centre over 10 years. Data for symptoms and signs, treatment, response, the development of complications (graded into four groups of severity) and outcome, were gathered. We identified characteristics particular to the elderly I.E. population compared to those of a younger age.

Results:
Of 107 patients, 50 were over 59 and 19 over 69 years of age. Risk factors for adverse outcome did not include age. Those over 69 more commonly had non-specific symptoms (e.g. weight loss and dyspnoea). Only of 37% the over 69 age group were treated surgically compared to 72% of those under 69. Across age groups the complication profile in surgically managed patients was higher than conservatively managed patients (since this is a higher risk subset). However, most strikingly, amongst the surgically managed patients, the outcomes in patients over 69 years compares well with all other age groups (Fig 1).

Conclusion:
The proportion of elderly patients treated surgically is lower than other age groups, reflecting understandable caution in surgical management of older patients. However, since the outcome in these patients compares favourably with all other age groups, we conclude that the surgical treatment of I.E. is an attractive option in carefully selected elderly patients.
Abstract 14343: Predictive Value of Myocardial Strain for Chimeric Antigen Receptor T-cell Therapy Associated Cardiovascular Events
Authors: Patel Nikita , Dalal Prarthana , Cascino Gregory , Sinha Arjun , Sunderraj Ashwin , Feinstein Matthew , Akhter Nausheen
Published: April 2024

Introduction:
Cardiovascular events following Chimeric Antigen Receptor (CAR) T-cell therapy are increasingly recognized. Left ventricular systolic dysfunction and arrhythmias are the most common cardiac toxicities seen. Thus, cardiac risk stratification in this population is important, especially in adults with subclinical cardiac disease. Although left ventricular global longitudinal strain (LV-GLS) has demonstrated prognostic utility for other cancer therapy related cardiac dysfunction, less is known regarding predictors of adverse cardiac events following CAR T-cell therapy. We determined the association of baseline LV-GLS with adverse cardiovascular events in adults receiving CAR-T cell therapy.

Methods:
We identified 75 patients who had baseline LV-GLS measurements available within 6 months of initiating CAR T-cell therapy at a large urban medical center from 2016-2020. Demographics, malignancy history, treatment data, cardiovascular risk factors, echocardiographic measurements (LV-GLS and left ventricular ejection fraction (LVEF)), and cardiac events were retrospectively collected via chart review. Absolute value of LV-GLS was used for ease of interpretation. Multivariable logistic regression was used to determine the association of LV-GLS (per 1% rise) with cardiovascular events with adjustment for age, BMI, CAD, HTN, HLD, DM, and previous cardiotoxic chemotherapy.

Results & Conclusions:
There were 10 CAR T-cell therapy-related cardiac events, including 1 death, 3 new/worsening cardiomyopathies, and 6 new/worsening arrythmias. Higher baseline LV-GLS (per 1% rise in absolute value) was associated with a significantly lower risk of cardiovascular events (OR 0.66, 95% CI 0.46, 0.96). These findings suggest LV-GLS may risk-stratify adults receiving CAR T-cell therapy for therapy-related cardiac toxicity. Additional prospective studies in other cohorts are needed to corroborate these findings.
Abstract 14346: High Intensity Exercise Increases Cardiorespiratory Capacity in a Preclinical Hypertrophic Cardiomyopathy Mouse Model
Authors: Herrera Jonathan J , Szczesniak Danielle , Szczesniak Kate , Gaur Pranjal , Manzo Miranda , Goddard Rose-Carmel , Yob Jaime , Tardiff Jil C , Day Sharlene
Published: April 2024

Introduction:
Patients with Hypertrophic Cardiomyopathy (HCM) who possess greater cardiorespiratory capacity (pVO
2
) are at lower risk for heart transplant and mortality. High intensity exercise (HIE) training used in cardiac rehabilitation for heart failure and cardiovascular disease results in superior increases in pVO
2.
The purpose of this investigation was to evaluate the effects of high intensity interval training (HIIT) on pVO
2
, as well as cardiac structural and functional parameters known to be altered by exercise in a transgenic cardiac troponin T (TG) HCM mouse model.

Methods:
Female and male C57BL/6J non-transgenic nTG (n=27) and TG (n=32) mice underwent a translationally parallel cardiac rehabilitation HIIT protocol. One treadmill training bout included 4-4 minute high intensity intervals (~80% preVO2 max speed) interspersed by 5-3 minute recovery intervals (~50% preVO2 max speed) for 31 total minutes. Bouts were repeated 3 times/wk for 6 wks. Pre and post HIIT pVO
2
and murine echocardiography were measured and analyzed by a blinded technician.

Results:
Following 6 weeks of the HIIT, nTG female (+13.5 mL/kg/min ± 3.6, p<0.01), nTG male (+13.5 mL/kg/min ± 3.6, p<0.01) and TG female (+7.06 ± 3.3 mL/kg/min, p<0.05) mice demonstrated an average increase in pVO
2
. TG male mice did not reach statistical significance (+4.34 ± p=0.12). Sedentary female (-15.9 mL/kg/min ± 3.3,p<0.001) and male (-13.1 mL/kg/min ± 3.9, p<0.01) TG control mice experienced a significant decrease in pVO
2
following the same period, while no change was observed in nTG sedentary controls. Independent of sex, nTG and TG HIIT mice had a significantly greater change in pVO
2
compared to sedentary counterparts. HIIT training did not result in changes to the following echocardiography measures in either nTG or TG mice: LV mass, LA volume, cardiac output, or stroke volume.

Conclusions:
Our results indicate that a translationally derived HIIT protocol improves cardiorespiratory capacity in HCM mice, absent of any adverse events or worsening of organ level disease pathology.
Abstract 14347: Sleep Apnea and Left Atrial Dilatation in Patients With Atrial Fibrillation Prior to Catheter Ablation
Authors: Tanaka Nobuaki , Okada Masato , Tanaka Koji , Hirao Yuko , Harada Shinichi , Iwakura Katsuomi , Fujii Kenshi , Okamura Atsunori
Published: April 2024

Introduction:
Sleep apnea and left atrial dilatation are both risk factors for an arrhythmia recurrence after catheter ablation (CA) of atrial fibrillation (AF). Negative intrathoracic pressure fluctuations during an obstructive apnea episode may cause the left atrium to distend and stretch its wall. Whether sleep apnea is associated with left atrial dilatation in patients receiving CA of AF remains unknown.

Methods:
This study was conducted under a retrospective, single-center, observational design. The data were derived from screening tests for sleep apnea, which were routinely performed in patients scheduled to receive CA of AF in our institution. After excluding patients who were already diagnosed with sleep apnea, we enrolled 1265 consecutive patients (age 65±11 years, 27.8% females, and 46.2% of non-paroxysmal AF) who underwent both home sleep apnea testing and multidetector computed tomography (MDCT) before the CA of AF. The severity of the sleep apnea was evaluated by the apnea-hypopnea index (AHI) using a watch-type peripheral arterial tonometry. Left atrial dilatation was evaluated by the left atrial maximum volume (LA max V) using 256-slice MDCT.

Results:
The age was 65±11 years, 27.8% were females, and 46.2% had non-paroxysmal AF. The mean AHI was 20.3±15.3 and LA max V 104.9±33.9 ml (R
2
=0.075, p<0.0001). LA dilatation, defined by an LA max V≥100 ml, was more frequently observed in patients with an AHI≥15 than those with an AHI<15 (62.5% vs. 40.2%, p<0.0001). We examined an LA max V≥100 ml as a predictor. After an adjustment by an advanced age (≥65 years), non-paroxysmal AF, male sex, obesity, hypertension, and congestive heart failure, all of which were significant predictors of an LA max V≥100ml in the univariate analysis, moderate or severe sleep apnea (AHI≥15) was a significant predictor of an LA max V≥100 ml (odds ratio 1.49, 95% confidence interval 1.13-1.97, p=0.0049).

Conclusion:
Among the patients scheduled to receive catheter ablation of AF, moderate or severe sleep apnea was independently associated with left atrial dilatation.
Abstract 14361: Time Restricted Feeding Modifies Day-Night Rhythms in Heart Rate and Cardiac Conduction
Authors: Ono Makoto , Burgess Don E , Seward Tanya , Elayi Claude S , Esser Karyn A , Schroder Elizabeth A , Delisle Brian P
Published: April 2024

Background:
Heart rate and cardiac conduction cycle with periodicity of 24-hours. The balance of circadian output from the autonomic nervous system and cardiomyocyte clock differentially regulates the sinoatrial (SA) and atrioventricular (AV) node, which could render the cardiac rate and conduction sensitive to internal misalignment and increase cardiac arrhythmogenicity.

Hypothesis:
The light-dark cycle entrains the circadian clock in the suprachiasmatic nucleus whereas the timing of feeding entrains circadian clocks in the peripheral organs. We determined whether time restricted feeding (TRF) to the light (inactive) cycle in mice caused misalignment in heart rate and conduction.

Methods:
Telemetry was used to record the electrocardiogram (ECG) in wild type (WT) mice housed in 12-hour light and 12-hour dark cycles. Day-night rhythms in ECG recordings were calculated by fitting data to a cosine function in ad libitum feeding conditions (ALF), 24 hours or 2-weeks after switching to TRF. Phase is reported as the peak rhythm relative to lights on (ZT = 0h).

Results:
During ALF, WT mice showed aligned 24-hour rhythms in the RR- and PQ-intervals that peaked at the beginning of the light cycle (ZT=4.4±0.5h and 4.6±0.3h, n=6). Switching to TRF for 24 hours caused a sudden and large phase shift in the peaks of 24-hour rhythms to the dark cycle (ZT=21.6±0.6h and 20.0±0.5h, p<0.05 compared to ALF). After 2 weeks of TRF, the RR- and PQ-intervals still peaked together at ZT=19.5±0.2h and 20.5±0.2h (p<0.05 compared to ALF). TRF also increased the 24-hour rhythm amplitude in the RR- and PQ-intervals by 161% and 118% after 24 hours of TRF, and by 109% and 80% after 2 weeks of TRF. That is due to significant increase peak of RR- (ALF 126.4 ± 2.6 ms, 24 hours after TRF 174.8 ± 7.3 ms, 2-weeks after TRF 167.2 ± 9.4 ms, p<0.01) and PQ-intervals (37.0 ± 1.3 ms, 41.5 ± 1.8 ms, 40.0 ± 1.1 ms, p<0.01) in dark cycle.

Conclusion:
TRF does not cause internal misalignment between the 24-hour rhythms of the RR- and PQ-intervals. TRF does cause a dramatic phase shift and increases the RR- and PQ-interval rhythm amplitudes along with their peak value. TRF could represent an underrecognized electrophysiological modifier in the day-night rhythms for heart rate and cardiac conduction.
Abstract 14363: Diabetes Duration and Subclinical Myocardial Injury: The Atherosclerosis Risk in Communities Study (ARIC)
Authors: Hamo Carine , Echouffo-Tcheugui Justin , Zhang Sui , Florido Roberta , Pankow James S , Michos Erin , Goldberg Ronald B , NAMBI VIJAY , Gerstenblith Gary , Post Wendy , Blumenthal Roger S , Ballantyne Christie M , Selvin Elizabeth , Coresh Josef , Ndumele Chiadi E
Published: April 2024

Introduction:
Diabetes exerts adverse effects on the heart, and a longer diabetes duration is associated with greater heart failure risk. The association of diabetes duration with subclinical myocardial injury is unknown.

Hypothesis:
Longer duration of diabetes is associated with a higher likelihood of myocardial injury, as reflected by elevated levels of high sensitivity cardiac troponin T (hs-cTnT).

Methods:
We performed a cross-sectional analysis of 9,243 participants without heart failure or coronary heart disease (mean age 63, 58% female, 20% Black) at ARIC Visit 4 (1996-98). Diabetes duration was calculated based on diabetes status at Visits 1 (1987-89) through 4, with additional use of self-reported age of diabetes diagnosis for those with a diagnosis prior to Visit 1. We used logistic regression to determine the association of diabetes duration with elevated (≥14 ng/L) and measurable (≥5 ng/L) hs-cTnT, adjusted for demographics and cardiovascular risk factors.

Results:
The prevalence of elevated hs-cTnT was higher in persons with longer diabetes duration, from 5% among those without diabetes, to 9% for those with diabetes 0-<5 years, up to 31% among those with diabetes for 15 years (p<0.0001). There was a robust association between longer diabetes duration and myocardial injury, with a diabetes duration of 15 years: adjusted OR 6.39 (95% CI 4.17-9.79) for elevated hs-cTnT compared to no diabetes (
Figure
). Diabetes duration of 15 years was also associated with measurable hs-cTnT (OR 2.83 [95% CI: 1.92-4.17], relative to no diabetes). Among those with diabetes, each additional 5 years of diabetes duration was associated with higher odds of elevated hs-cTnT (OR 1.46, 95% CI 1.35-1.57).

Conclusions:
Longer diabetes duration is strongly associated with subclinical myocardial injury. Interventional studies are needed to assess whether prevention and delay of diabetes onset can mitigate early myocardial damage.
Abstract 14371: Incidence of Cardiogenic Shock in In-Hospital vs Out of Hospital ST-elevation Myocardial Infarction
Authors: Nair Raunak , Kassis Nicholas , Kumar Anirudh , Huded Chetan P , Johnson Michael J , Kravitz Kathleen A , Reed Grant W , Krishnaswamy Amar , Menon Venu , Lincoff A M , Meldon Stephen , Kralovic Damon M , Kapadia Samir R , Khot Umesh N
Published: April 2024

Background:
Cardiogenic shock (CS) remains the most common cause of death in patients with acute myocardial infarction. We aimed to study if the incidence of CS is different in patients who develop in-hospital STEMI compared to patients admitted with out-of-hospital STEMI (Direct STEMI).

Methods:
All STEMI patients who underwent Percutaneous Coronary Intervention (PCI) at the Cleveland Clinic main campus between January 1, 2011, to July 15, 2019, were included in our study. Patients were classified depending on the location of STEMI into in-hospital or out of hospital (direct STEMI) and the incidence of cardiogenic shock was compared between both the groups.

Results:
There were a total of 1715 patients who were admitted to our hospital with STEMI from outside (direct STEMI) compared to 132 patients who developed in-hospital STEMI. Baseline characteristics were quite similar except for a higher prevalence of smoking in the direct STEMI group and a higher prevalence of prior PCI and prior heart failure in the in-hospital STEMI group. We found that 25.8% of patients with In-hospital STEMI developed cardiogenic shock whereas only 7.9% of patients with direct STEMI developed cardiogenic shock.

Conclusion:
Patients with in-hospital STEMI are three times more likely than direct STEMI patients to develop cardiogenic shock. Integration of therapeutic strategies around cardiogenic shock may be important in improving outcomes of this high-risk group of patients with STEMI.
Abstract 14381: High Coronary Artery Calcium Score Predicts Earlier and More Frequent Need for Cardiac Revascularization - A Large Scale, Single Center Study
Authors: coy kevin , Varga Zoltan , Rynders Beatrice , Sjovold Alexander , Stys Veronica , Petrasko Mark , Petrasko Phillip , Pham Melissa , stys patryk , Singh Komaldeep , singh Aditya , Saad Shaukat Muhammad Hamza , Hajek Catherine , Sincan Murat , Petrasko Marian S , Stys Adam , Stys Tom
Published: April 2024

Introduction:
Coronary artery calcium score (CAC) predicts the risk of cardiac events with need of revascularization. CAC scores indicate plaque burden and are classified as low (<100), moderate (100-399) or high (≥400).

Hypothesis:
High CAC score predicts earlier and more frequent need for cardiac revascularization (CABG or PCI) compared to low CAC score.

Methods:
A total of 60,719 subjects were screened for CAC score from which 1,861 underwent subsequent coronary revascularization if clinically indicated. Patients with moderately elevated CAC scores were excluded from the analysis. The incidence and timing of revascularization was compared between the low and high CAC score groups using two sample Z test. Wilcoxon rank sum test was used to calculate medians.

Results:
The analysis included 47 937 patients in the low CAC score group (mean age of 53.6 ± 9.9 with 59.5% female) and 5415 in the high CAC score group (mean age of 64.8 ± 8.4 with 28.2% female). As shown in Table 1, the incidence of cardiac revascularization was significantly higher in the high CAC score group (p < .0001). Average time to intervention was significantly shorter in the high CAC score group (p < .0001).

Conclusions:
Significantly higher rates of cardiac revascularization were observed in patients with high CAC score. In these individuals, the average time to revascularization was found to be lower than in the low CAC group. Low CAC score individuals had nearly double the time to an event, which is a finding with potentially high clinical significance.
Abstract 14383: Medical Therapy Before, During, and After Hospitalization in Medicare Beneficiaries With Heart Failure and Diabetes: The Get With the Guidelines - Heart Failure Registry
Authors: Bhatt Ankeet S , Fonarow Gregg C , Greene Stephen J , Holmes DaJuanicia N , Alhanti Brooke , Devore Adam D , Butler Javed , Heidenreich Paul A , Huang Joanna , Kittleson Michelle M , Joynt Maddox Karen E , McDermott James J , Owens Anjali T , Peterson Pamela , Solomon Scott , Vardeny Orly , Yancy Clyde W , Vaduganathan Muthiah
Published: April 2024

Introduction:
Patients with heart failure with reduced ejection fraction (HFrEF) and diabetes mellitus (DM) are at risk for worsening HF events, yet little is known about therapeutic changes surrounding hospitalization. We aimed to characterize use of medical therapies before, during, and after hospitalization for HF.

Methods:
We identified Medicare beneficiaries in the GWTG-HF registry with HFrEF and DM who were hospitalized between July 2016 and September 2017 and had Part D prescription coverage for ≥6 months before and ≥3 months after hospital discharge. Medication fills for evidence-based HFrEF and antihyperglycemic therapies were assessed at 6 and 3 months before hospitalization, at hospital discharge, and 3 months post-discharge.

Results:
Among 3,272 Medicare beneficiaries with HFrEF and DM, mean age was 77±7y, 41% were women, and 15% were Black. Overall, 92%, 56%, 28%, and 6% were prescribed β-blocker, ACEi/ARB, MRA, and ARNI at discharge. Rates of all therapies were higher at discharge than immediately prior to hospitalization, though rates of β-blocker and ACEi/ARB use declined 3-months post-discharge. ‘Triple therapy’ (ACEI/ARB/ARNI+β-blocker+MRA) was prescribed in 9% prior to hospitalization and 20-21% at discharge and early-post-discharge. After hospitalization, insulin was prescribed most frequently (35%), followed by metformin (21%), sulfonylureas (19%), and DPP4i (11%), while GLP-1RA (2%) and SGLT2i (0.5%) use was infrequent. Modest changes in antihyperglycemic therapies were observed pre- vs. post-hospitalization, including an increase in insulin from 32% to 35% and decrease in metformin from 26% to 21% and SGLT2i from 0.8% to 0.5%.

Conclusions:
Despite modest improvements in use of evidence-based therapies for HFrEF during and shortly after hospitalization for HF, only 1 out of 5 patients are treated with comprehensive medical therapy. Early adoption in 2016-2017 of SGLT2i was low in a high-risk population with comorbid HFrEF and DM.
Abstract 14395: Transcriptomes of Thrombi Retrieved by Mechanical Thrombectomy Can Distinguish Ischemic Stroke Subtypes
Authors: Tutino Vincent M , Fricano Sarah , Waqas Muhammad , Siddiqui Adnan H , Poppenberg Kerry E
Published: April 2024

Introduction:
Determination of stroke etiology is crucial for prevention of secondary ischemic events. Diagnostic workups are intensive and expensive, and in cryptogenic cases are fruitless.

Hypothesis:
We hypothesize that thrombi from strokes of different etiologies have unique transcriptomic profiles.

Methods:
In 76 patients undergoing mechanical thrombectomy, we collect retrieved thrombi and extracted RNA on the PerkinElmer Chemagic 360. 48 samples of sufficient quality underwent 100-cycle, paired-end RNAseq on the Illumina NovaSeq6000. Transcriptomes with < 10M assigned reads were excluded; counts were normalized by transcripts per million. Significant differentially expressed genes (DEGs) between stroke subtypes (defined by Trial of Org 10172 in Acute Stroke Treatment) were identified by a false discovery rate-corrected F-test (q-value)<0.05 and an absolute fold-change>2. Bioinformatics and gene ontology enrichment analyses were performed to understand the pathobiology of DEGs.

Results:
We analyzed transcriptomes from 38 thrombi; 6 large artery atherosclerosis (LAA), 20 cardioembolism (CE), 5 other vasculopathy (OV), and 7 cryptogenic. Comparing CE to LAA, we found 218 DEGs that were related to greater Immune System Processes, Coagulation, and Regulation of Macrophage Activation. OV vs. LAA showed 414 DEGs, which reflected increased Regulation of Wound Healing, Biological Adhesion, and Cell Migration. Comparing CE to OV revealed 341 DEGs that were related to increased Cell Activation and Leukocyte Activation. Principal component analysis showed separation between these subtypes and that cryptogenic samples may be related to CE or OV.

Conclusion:
Transcriptomes of stroke thrombi can delineate etiology. CE thrombi are more inflammatory, while OV thrombi reflect wound healing responses. Cryptogenic thrombi may be related to multiple etiologies.
Abstract 14404: Developing a Frailty Score for Use in Children and Adolescents With Congenital Heart Disease
Authors: Studyvin Sarah , Birnbaum Brian F , Staggs Vincent , White David A
Published: April 2024

Introduction:
Frailty is a complex syndrome that is associated with morbidity and decreased quality of life. It consists of 5 constructs: slowness, weakness, fatigue, energy expenditure, and body composition. Although frailty has been investigated in geriatrics, there is little describing the association of a frailty score on health outcomes in children and adolescents with chronic disease. The purpose of the study is to create a frailty score for use in children and adolescents and evaluate its usefulness in predicting morbidity in those with congenital heart disease (CHD).

Hypothesis:
We hypothesize that a higher composite frailty score is associated with an increased incidence in poor clinical status.

Methods:
Participants (Fig 1A) were enrolled in a cross-sectional study comparing the 5 components of frailty to age and sex matched controls. Frailty measures were modified for children and adolescents (Fig 1B). Constructs were combined to form a composite frailty score, which was correlated to clinical status, characterized as number of hospitalizations, emergency room (ER) visits, number of heart failure medications, at 23-31 month follow up.

Results:
The association between composite frailty scores, individual frailty measures, and outcomes was evaluated using Pearson correlation coefficient (Fig 1B). A higher frailty score was not found to be significantly correlated with outcomes. However, all individual frailty measures excluding body composition were inversely associated with the outcomes, indicating worse outcomes with poor functional status.

Conclusions:
Although composite frailty score was not associated with clinical outcomes, individual constructs were associated with worse clinical status. Our study was limited by a small and heterogenous sample, and future studies should be done to validate a frailty score for use in the CHD population. A frailty tool can identify at risk patients in this vulnerable population prior to sentinel events.
Abstract 14410: Predicting Intubation and Ventilation Needs Upon Admission for Intensive Care Patients With Congestive Heart Failure
Authors: Sangari Ayush , Sood Aditya , Sangari Anish , Sood Nitish , Maini Kushagara
Published: April 2024

Introduction:
Congestive heart failure (CHF) is one of the most common diagnoses for patients admitted to an intensive care unit (ICU), and intubation or ventilation may be necessary to combat severe associated respiratory symptoms. Current guidelines give high-level recommendations to intubate patients with a Glasgow Coma Scale (GCS) score of 8 or lower. However, prior studies have shown that a large portion of patients who were ultimately intubated had GCS scores greater than 8, demonstrating the need for a better tool to predict the necessity of intubation. The present study sought to build machine-learning (ML) models that could predict the need for intubation or ventilation for CHF patients upon ICU admission.

Methods:
5,623 patients (of which 1,058 were intubated and 2,816 were ventilated) in the eICU Collaborative Research Database who underwent screening using the Acute Physiology and Chronic Health Evaluation and were diagnosed with CHF were used to train (50%) and test (50%) the ML models. Gender, age, treatment status, readmission status, medication status upon admission, GCS motor score upon admission, and GCS eyes score upon admission were used as feature inputs for the ML models, which were classic three-layer neural networks. For intubation, the ML model performance was compared against using the common heuristic of intubating patients with a GCS score of 8 or less.

Results:
The ML model for intubation upon admission prediction had an accuracy of 84.8% and an area under the receiver operating characteristic curve (AUC) of 0.79. Meanwhile, using the aforementioned heuristic for intubation prediction yields an accuracy of 85.7% (AUC n/a). A second ML model was trained to predict the need for ventilation upon admission and had an accuracy of 71.2% and an AUC of 0.80.

Conclusion:
This newly developed ML model for intubation demonstrates relative success in predicting intubation needs for patients with CHF upon ICU admission. In addition, this model performs similarly to currently accepted guidelines. Further improvement and a larger dataset could better train the model to provide more accurate predictions. Such predictions could help support medical decision-making and resource allocation planning.
Abstract 14418: Epigenetic Landscapes of Stroke Risk Haplotypes Suggest Genetic Risk Operates Through Fibroblasts
Authors: Poppenberg Kerry E , Kuo Cathleen , Waqas Muhammad , Siddiqui Adnan H , Jarvis James N , Tutino Vincent M
Published: April 2024

Introduction:
Genome-wide association studies (GWAS) in stroke have identified many single nucleotide polymorphisms (SNPs). However, the mechanisms behind how these SNPs confer genetic risk is unknown.

Hypothesis:
Stroke variants confer genetic risk by affecting non-coding DNA elements, specifically enhancers, that modulate gene expression in certain cell types.

Methods:
We analyzed 26 stroke risk SNPs that were validated across multiple studies. We mapped these SNPs to the associated linkage disequilibrium (LD) blocks and used chromatin immunoprecipitation-sequencing data to examine the presence of enhancer-associated histone marks (H3K27ac, H3K4me1, H3K9ac) in each block. This was performed using data for cells of the circulating blood and the vascular tissue (significant enrichment was determined by empirical p-value calculation). In cells with significant enhancer marks, HiC data was used to identify topologically associated domains (TADs) encompassing the LD blocks, which contain genes potentially affected by altered enhancer activity. Disease and biological function term enrichment was performed in Ingenuity Pathway Analysis to investigate the biological significance of these genes.

Results:
Fibroblasts and smooth muscle cells demonstrated significant enrichment of enhancer-associated histone marks in stroke-associated LD blocks (p<0.05). Bioinformatics analysis on TAD genes reflected enrichment of vessel development (e.g., Angiogenesis, Vasculogenesis) and fibroblast turnover (e.g., Proliferation of Fibroblast Cell Lines, Apoptosis of Fibroblast Cell Lines).

Conclusion:
Stroke-associated genetic variants confer risk through the vessel wall rather than circulating immune cells. Further studies are needed to experimentally confirm function of these enhancers and identity of causal variants.
Abstract 14428: The Effect of Menopause on Coronary Blood Flow in Females Presenting With Angina and Non-Obstructive Coronary Artery Disease
Authors: Ahmad Ali , Ozcan Ilke , Toya Takumi , Corban Michel , Sara Jaskanwal D , Lerman Lilach , Lerman Amir
Published: April 2024

Introduction:
Changes in coronary artery diameter (CAD) and coronary blood flow (CBF) in reaction to acetylcholine are important surrogates of endothelial health, and abnormalities in these parameters might represent early atherosclerosis. Menopause is associated with an increased risk of coronary artery disease, yet the role of menopause on the endothelium is not well described.

Hypothesis:
The vasodilatory response of the endothelium to acetylcholine (Ach) decreases after menopause.

Methods:
A total of 1271 (42% pre-menopausal) females with angina and non-obstructive coronary artery disease (<50% angiographic stenosis) that underwent coronary reactivity study were enrolled. A doppler wire was positioned and incremental Ach doses were injected (10
-6
, 10
-5
, and 10
-4
mol/L). CBF was then calculated from CAD and doppler-derived flow velocity. Comparisons between the pre-and post-menopause groups were performed.

Results:
Mean age of the pre-menopausal group was 44±10 years, while that of the post-menopausal 59±9 years. Pre-menopausal females had higher baseline CAD as compared to post-menopausal females (2.22 [1.90; 2.65] vs. 2.20 [1.85; 2.55] mm, P=0.03). However, this difference was nullified with subsequent doses of Ach
(Figure 1A&B
). Pre-menopausal females had a higher baseline CBF than post-menopausal females (32.1 [21.7; 44.9] vs. 29.2 [19.8; 42.0] mL/min; P=0.01). This difference progressively increased with successive doses of Ach (10
-4
:49.5 [30.3; 77.0] vs. 41.7 [24.4; 69.0] mL/min; P=0.0002), revealing a greater microvascular vasodilatory response in pre-menopausal females (Cumulative %ΔCBF after highest dose= 60 [2.6; 122] vs 45 [-4; 98], P=0.002) (
Figure 1C&D
).

Conclusions:
Premenopausal females have greater sensitivity of the microvascular endothelium to Ach compared to post-menopausal, suggesting a possible role for estrogen in mediating the effect of stress on the microvasculature through the endothelium.
Abstract 14429: Clinical and Laboratory Correlates of Impaired Cholate Clearance in the Adult Fontan
Authors: Kim Yuli Y , Saef Joshua , Everson Greg , Helmke Steve , Carducci Jessica , Glatz Andrew C , Partington Sara L , Ruckdeschel Emily , Rychik Jack , Hoteit Maarouf
Published: April 2024

Introduction:
The dual cholate test is a noninvasive, flow-dependent assay measuring hepatic clearance of bile acid, cholate. A measure of liver function, cholate clearance has been shown to be decreased in the Fontan. We aim to explore the association between clinical features, cardiac/liver testing, laboratory tests and cholate clearance in a cohort of Fontan patients.

Methods:
Single center, prospective study of Fontan patients ≥ 18 years. Hepatic clearance of orally administered d4-cholate and intravenously administered 13C-cholate were measured in peripheral venous samples and calculated as portal hepatic filtration rate (HFR), systemic HFR, shunt fraction (systemic HFR/portal HFR), and disease severity index (DSI). Subjects were grouped according to shunt fraction (abnormal >30%) and/or DSI (abnormal >18.3). Kruskall-Wallis and Fisher exact tests were performed to analyze between-group differences.

Results:
Twenty-four Fontan patients were enrolled (50% female, median age 30.3 [interquartile range IQR 25.0 - 36.5] years, median cardiac index 2.91 [IQR 2.50 - 3.24] ml/mg/m2). Median total bilirubin was 0.95 [IQR 0.6 - 1.2] mg/dL, AST 29.5 [IQR 21.0 - 38.3] U/L, ALT 26.5 [IQR 20.8 - 36.3] U/L, alkaline phosphatase 75.5 [IQR 68.3 - 94.8] U/L, albumin 4.6 [IQR 4.3 - 4.7] g/dL, alpha fetoprotein 2.0 [1.9 - 3.0] ng/mL, platelets 177 [IQR 142.8 - 189.3] 10
3
/μL. There were no subjects with abnormal shunt fraction and normal DSI (Table).

Conclusions:
Oxygen saturation, alkaline phosphatase, and alpha fetoprotein correlate with abnormal cholate clearance whereas cirrhosis on imaging and Fontan pressures trended towards an association. Larger studies are warranted to explore these associations with cholate clearance to elucidate the nature of Fontan associated liver disease.
Abstract 14476: Effects of Encaleret on Corrected QT Interval in Autosomal Dominant Hypocalcemia Type 1: Early Results From an Ongoing Phase 2b, Open-Label, Dose-Ranging Study
Authors: Hartley Iris , Gafni Rachel , Roszko Kelly , Pozo Karen , Collins Michael T , Nemeth Edward , Sani-Grosso Ramei , Sridhar Ananth , Stapleton Lyndsay , Roberts Mary Scott , Fox Jonathan
Published: April 2024

Introduction:
Autosomal dominant hypocalcemia type 1 (ADH1) is caused by gain-of-function variants of the calcium-sensing receptor (CaSR) gene, resulting in receptor proteins with increased sensitivity to extracellular calcium. Individuals with ADH1 exhibit hypocalcemia, hypomagnesemia, hyperphosphatemia, and inappropriately low levels of PTH. Hypocalcemia and hypomagnesemia can slow cardiac repolarization and potentially prolong the QT interval in patients with ADH1. Prolongation of the QT interval can lead to potentially malignant ventricular arrhythmias. Calcilytics are antagonists of the CaSR with the potential to restore normal CaSR sensitivity in ADH1 and thereby normalize blood levels of calcium and magnesium. This study investigated the biochemical and ECG effects of encaleret, an investigational oral calcilytic, in individuals with ADH1.

Methods:
CLTX-305-201 [NCT04581629] is a 3-period, open-label, dose-ranging study of encaleret in adults with ADH1. In Period 1, supplements were discontinued 1 or 2 days prior to administering sequential, increasing daily doses of encaleret over 5 days with frequent biochemical monitoring. Standard 12-lead surface ECGs were recorded at baseline (BL) and on Day 5 (D5).

Results:
Data (mean±SD) from the first 6 participants are presented. BL and D5 values were compared as follows: •
PTH:
BL 3.4±4.5; D5 64.8±49.6 (nl 10-65 pg/mL; p<0.01) •
Albumin-corrected total calcium:
BL 7.6±0.6; D5 9.0±0.5 (nl 8.4-10.2 mg/dL; p<0.01) •
Magnesium:
BL 1.6±0.4; D5 2.0±0.5 (nl 1.6-2.6 mg/dL; p<0.01) •
Phosphate:
BL 4.5±0.7; D5 2.9±0.5 (nl 2.3-4.7 mg/dL; p<0.01) •

QT
c
B:

BL 452±9; D5 433±11 (nl <440 msec; p<0.01) There were no important changes or trends in heart rate, blood pressure, or other ECG intervals. Encaleret was well-tolerated and without serious adverse events.

Conclusion:
Hypocalcemic ADH1 study participants experienced abnormal cardiac repolarization manifested as prolongation of the QT interval at baseline. The consistent responses following encaleret treatment ADH1 participants provide preliminary evidence that encaleret, by raising blood levels of calcium and magnesium, may normalize cardiac repolarization in patients with ADH1. Longer-term evaluation of encaleret in ADH1 is ongoing.
Abstract 14488: Modifiable Risk Factor Burden Among Young Adults With Heart Failure
Authors: jain vardhmaan , Gupta Kartik , Vaduganathan Muthiah
Published: April 2024

Background:
Recent population data have suggested that HF may be presenting at younger ages. Little is known about the relative importance of traditional prognostic factors in this growing cohort.

Methods:
We analyzed data of 1,071 participants aged ≥ 18 years with self-reported HF enrolled in 6 cycles of NHANES from January 1, 1999 to December 31, 2010. We describe mortality trajectories through median follow-up of 6.7 ± 4.3 years by age group (young [n=154] 18-54y; middle [n= 190] 55-65y; and older [n=727] >65y). Multivariable Cox proportional hazards models were constructed to determine if age, gender, hypertension, diabetes, obesity, smoking, and eGFR differentially associate with mortality across age groups using interaction testing.

Results:
Younger patients with HF were more often Black, had better kidney function, and had higher rates of diabetes, obesity, and smoking than middle-age and older adults. Age modified the association of obesity and diabetes on subsequent risk of mortality such that diabetes was associated with higher mortality risk in young (adj HR 2.11; 95% CI: 1.04 -4.31) and middle-aged adults (adj HR 2.18; 95% CI: 1.34- 3.57) as compared with older adults (adj HR 1.27; 95% CI: 1.04-1.55); P-interaction<0.05. Similarly, obesity was associated with higher risk of mortality in younger (adj HR 2.07; 95% CI: 1.02-4.22) compared with middle-aged (adj HR 0.61; 95% CI: 0.37- 1.01) and older adults (adj HR 1.03; 95% CI: 0.85-1.26); P-interaction<0.05. Predictive accuracy of multivariable models declined with increasing age, with a Harrel’s C- statistic of 0.71 in young, 0.67 in middle-aged, and 0.66 in older adults.

Conclusion:
Modifiable risk factors such as obesity and diabetes are more common in younger adults with HF and may have greater relative importance in forecasting subsequent mortality than in middle-aged and older adults. These data underscore the need for treatment approaches targeting these core risk factors earlier in life.
Abstract 6935: DOACs Use in Very Elderly AF Patients After TAVR Confers Significant Risk of Thromboembolic Events
Authors: Cerrud-Rodriguez Roberto C , Wiley Karlo A , castillero isabella , Goodwin Ashley , Saralidze Tinatin , Villablanca Pedro A , Gonzalez Maday , Terre Juan , Wiley Jose , Di Biase Luigi
Published: April 2024

Introduction:
To assess the efficacy and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKA) in very elderly patients with atrial fibrillation (AF) undergoing transcatheter aortic valve replacement (TAVR). Two efficacy outcomes were used: all-cause mortality and thromboembolic events (defined as stroke and/or transient ischemic attack and/or systemic embolism and/or valve thromboses) and one safety outcome: life-threatening or major bleeding events. There is a discrepancy between the results of previous studies on the appropriate anticoagulation regimen in patients with AF with CHA
2
DS
2
Vasc score≥2 undergoing TAVR

Methods:
A systematic review of Medline, Cochrane, and Embase was done to find all studies in which the previously described outcomes in AF patients undergoing TAVR were compared according to their use of DOACs vs. VKA.

Results:
Six studies with a total 3,631 participants, mean follow-up 19±9.4 months (male: 30.3%, mean ages were 82.8±1.1 years and 82.2±1.5 years for the DOAC and the VKA groups, respectively) were included in our analysis. No significant differences were found between the DOAC and VKA group in all-cause mortality (Risk Ratio [RR] 1.06, 95% Confidence Interval [CI] 0.84-1.35) or life-threatening or major bleeding events (RR 1.02, 95% CI 0.83-1.25). A significant increase in risk of thromboembolic events was found in the DOAC group (RR 1.23, 95% CI 1.05-1.44).

Conclusions:
VKA should be preferred over DOACs in very elderly patients with AF who undergo TAVR, given the significantly increased risk in thromboembolic events seen with DOACs and the lack of significant difference in all-cause mortality and bleeding. RCTs are needed to confirm or refute our findings.
Abstract 6937: Atrial Fibrillation in Breast Cancer Patients: Incidence, Prevalence, Risk Factors, and Mortality: Longitudinal Seer-Medicare Analysis
Authors: Guha Avirup , Fradley Michael , Dent Susan F , Weintraub Neal L , Lustberg Maryam , Alonso Alvaro , Addison Daniel
Published: April 2024

Background:
The national incidence, risk factor, and associated mortality of atrial fibrillation (AF) in early or advanced breast cancer patients are unknown.

Methods:
Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified females, ≥ 66-year-old, with a new primary diagnosis of breast cancer from 2007 through 2014. These patients were individually matched 1:1 to Medicare enrollees without cancer, and each pair was followed for one year to identify a primary outcome of AF. Cumulative incidence rates were calculated using competing risk survival statistics. Following this, risk factor analysis was conducted using the adjusted Cox proportional hazards model. Finally, Kaplan-Meier methods and adjusted Cox proportional hazards modeling were performed to estimate mortality in breast cancer patients with incident and AF prior to breast cancer diagnosis.

Results:
This study included 85,423 breast cancer patients. Among these 9,425 (11.0%) had AF diagnosis prior to the breast cancer diagnosis. New AF was diagnosed in 2,993 (3.9%) patients in a 1-year period after the breast cancer diagnosis [incidence rate = 3.3% (95% CI = 3.0% - 3.5%) at 1-year; highest rate in the first two months (0.6%/month)]. The population standardized AF incidence was higher in Black compared to White females (58.8 vs. 49.9 per 1000 person-years in 2014, respectively). Apart from traditional demographic and cardiovascular risk factors, breast cancer stage was strongly associated with development of AF [AJCC Stage II vs. I: adjusted HR (aHR)= 1.51 (95% CI= 1.37 - 1.65); AJCC Stage III vs. I: aHR= 2.63 (95% CI= 2.35 - 2.94); AJCC Stage IV vs. I: aHR= 4.21 (95% CI= 4.04 - 5.48)]. New onset AF after breast cancer diagnosis [aHR = 3.51 (95% CI = 1.69 - 7.32)] and AF prior to breast cancer diagnosis [aHR = 1.70 (95% CI = 1.26 - 2.29)] was associated with increased 1-year- cardiovascular mortality.

Conclusion:
AF incidence is significantly higher in women after a breast cancer diagnosis. Apart from traditional risk factors, higher breast cancer stages at diagnosis are significantly associated with a higher risk of AF. New or prior AF in the setting of new breast cancer increases 1-year cardiovascular mortality.
Abstract 6943: Ablation Index-guided Pulmonary Vein Isolation Improve Performance and Safety of Treatment of Atrial Fibrillation
Authors: Zou Cao , Sun Si-jia , Hu Ming-Sheng
Published: April 2024

Introduction:
Pulmonary vein isolation (PVI) is a pivotal therapy for treatment of atrial fibrillation (AF), especially paroxysmal AF. Previous studies suggest that ablation index (AI) which integrated contact force (CF), time and power in a weighted formula improved success rate and safety of PVI.

Hypothesis:
Recently, our group has raised a novel protocol of AI-guided AF ablation according to different wall thickness of left atrium and compared the performance and safety of VisiTag ablation with or without this AI strategy.

Methods:
In this retrospectively study, AI parameters were set as 300-380U, 400-450U, 380-400U, 380-400U and 450-500U for posterior, anterior, inferior, roof and ridge respectively (
Figure 1
). Radiofrequency energy was delivered at a maximum power output of 25-35 W depending on the ablation site (25-30W for the posterior aspects of the right and left PVs and 30-35 W for the anterior, inferior, Roof and ridge aspects).

Results:
No significant difference of patient characteristics was observed in VisiTag+AI group versus VisiTag group. One year after the procedure, the overall success rate was higher in VisiTag+AI group as compared to VisiTag group without differentiation of paroxysmal AF and persistent AF (95.1% vs. 83.3%, P=0.02). In subgroup analysis, the 1-year success rate in paroxysmal AF patients were 95.5% versus 82.5% in VisiTag+AI group versus VisiTag group (P=0.03), whereas the 1-year success rate in persistent AF patients were 93.3% versus 84.6% in VisiTag+AI group versus VisiTag group (P=0.40).Only one case of minor pericardial effusion without additional management was observed in VisiTag+AI group, whereas two cases of minor pericardial effusion and one case of pericardial tamponade were observed in VisiTag group during perioperative care.

Conclusions:
Improved performance and safety was observed in VisiTag ablation with this novel AI strategy in paroxysmal AF patients.
Abstract 6950: Precision Quantification of Cardiac Biomarkers Using Reagent-Free Electrochemical Aptasensors
Authors: Mahmud Alam , Das Jagotamoy , Chang Dingran , Gomis Surath , Chen Jenise , Yousefi Hanie , Sargent Edward H , Kelley Shana O
Published: April 2024

Introduction:
Precision quantification of cardiac biomarkers in unprocessed patient samples could reveal critical information in the event of acute myocardial infarction and chronic heart failure. Consequential research efforts have been made in recent years to develop self-contained analytical devices for accurate and rapid quantification of molecular analytes in unprocessed biological fluids, however, their poor sensitivity and compromised robustness in complex biofluids greatly limit their clinical usability. We aimed to investigate the utility of a new biomolecular analysis technique for accurately quantifying BNP and NT-pro BNP directly in whole blood using only a sensor-modified electrode chip.

Methods and Results:
Recently, we have developed a new class of reagentless biosensors using a molecular pendulum (MP) for monitoring physiologically relevant proteins directly in unprocessed body fluids. The sensing strategy is based on the kinetics of a MP tethered to an electrode surface where the motion of the MP is modulated by the presence of target analyte. Using an antibody as the bioreceptor unit, our MP sensors demonstrated to detect 1 pg/mL of cardiac troponin I in several bio-fluids. Since aptamers hold great promise for developing next-generation of diagnostics and therapeutic tools, we employed them to develop reagent-free MP aptasensors that quantify different heart failure biomarkers including BNP and NT-pro BNP directly in whole human blood. Our MP aptasensors show excellent performance matrices, such as a wide dynamic range (10 fg/mL to 10 ng/mL of BNP), a limit of quantification of 93.5 fg/mL, excellent specificity, and long-term stability, measured directly in whole human blood. Moreover, the analytical resolving capability of the sensors can distinguish samples that differ by only 20 pg/mL of BNP, which is critical for the BNP guided therapy for heart failure. We were also able to quantify BNP and NT-pro BNP simultaneously from the same sample by multiplexing the sensors on the same electronic chip.

Conclusion:
The analytical strength of our reagent-free MP aptasensors warrants their accelerated development as they could play crucial roles for earlier identification and better risk stratification of heart failure patients.