bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4146493: 84 Immune checkpoint profiling in major aortic diseases leads to identification of potential roles of CD155-CD206 pathway in suppressing inflammation and immune responses
Authors: Shao Ying , Saaoud Fatma , Xu Keman , Lu Yifan , Jiang Xiaohua , Hong Wang , Yang Xiaofeng
Published: November 2024

Immune checkpoints are a group of immune regulatory plasma membrane proteins expressed on antigen-presenting cells and T cells, which are crucial for maintaining self-immune tolerance and modulating the effectiveness of T cell immune responses. The importance of selected immune checkpoints in cardiovascular diseases have been widely recognized. However, we identified a significant knowledge gap in the comprehensive understanding of immune checkpoint signaling across multiple levels in cardiovascular diseases. To bridge this gap, we developed a framework that encompasses disease stages and cell types regulated by immune checkpoint axes within the contexts of three major aortic diseases such as abdominal aortic aneurysm, atherosclerosis, and diabetic aortic pathology. Initially, at the transcriptional level, we analyzed the expressions of 58 pairs of immune checkpoint genes in mouse aorta across three models of abdominal aortic aneurysm, four models of hyperlipidemia and atherosclerosis, and three models of diabetes, each representing various stages of the respective diseases. At the single-cell level, we investigated the gene enrichment within separate clusters of aortic cells under diseased conditions. From the results, we found that among the immunosuppressive or double functional immune checkpoints, CD155 expression patterns were different from that of CD274 in more than 50% samples, suggesting that CD155 may play immunosuppressive/anti-inflammatory roles in aortic diseases that are different from CD274. Therefore, we performed flow cytometry to investigate potential regulation of the TIGIT/CD155 axis at the cellular levels in four organs of ApoE-/- mice compared to wild type. The results identified that TIGIT/CD155 axis is upregulated in aortic CD45+ leukocytes but not in CD45- non-leukocyte cellular compartments. CD155 enrichments were identified in CD45+CD11b+CD11c+ cells in blood and kidney, as well as in CD45+CD11b-CD11c+ cells in the lung. Furthermore, among the three functional markers used to identify the subclusters of heterogeneous aortic antigen-presenting cells—CD206, CX3CR1, and CD103—positive correlations were observed between CD155 expressions and the anti-inflammatory marker CD206, while correlations with CX3CR1 and CD103 were absent. These results have demonstrated that CD155-CD206 pathway may play surrogative roles to CD274 in suppressing inflammation and immune responses in atherosclerosis and aortic diseases.
Abstract 4146592: Device-Recorded Physical Activity and Atrial Fibrillation Burden: A Natural History Experiment from the COVID-19 Pandemic in the TRIM-AF Clinical Trial
Authors: Kim Hyun Su , Sun Han , Wass Sojin , Telfer William , Schilling Taylor , Lissemore Frances , Bibidakis Dimitra , Lin Cheryl , Yang Lucy , Sullivan Erin , Jin Alison , Guo Lydia , Foster Parker , McHale Meghan , Crookshanks Michael , Cantlay Catherine , Cantlay Paul , Hussein Ayman , Cho Leslie , Nissen Steven , kashyap sangeeta , Van Iterson Erik , Bruemmer Dennis , Mehra Reena , Smith Jonathan , Varma Niraj , Van Wagoner David , Barnard John , Chung Mina
Published: November 2024

Introduction:
Low physical activity (PA) has been identified as a risk factor for development of atrial fibrillation (AF). However, the effect of changes in PA on directly recorded AF burden has not been well studied. The COVID-19 pandemic offered an opportunity to observe whether changes in activity were correlated with changes in AF burden. To determine if reduced PA is associated with higher AF burden, we assessed daily PA and AF burden data from patients with cardiac implantable electronic devices (CIEDs) enrolled in a prospective clinical trial, Targeting Risk Interventions and Metformin for Atrial Fibrillation (TRIM-AF, NCT03603912).

Methods:
Daily AF burden and activity were determined from implantable cardiac devices with atrial leads. The pandemic lockdown period was analyzed for up to 1 year. Pre-pandemic periods were matched by month to pandemic periods. To test the potential confounding of aging, pre-pre-pandemic periods were matched by month to pre-pandemic periods. To reduce the confounding of study interventions, matched periods were taken on one side of the study enrollment date. For PA and AF burden, Gaussian linear mixed models and a Bayesian mixed effect model were fitted and adjusted for age, sex, and device manufacturers. A Gaussian model was used to correlate daily activity minutes and AF%. Time splines were added to adjust for non-linear time effects. Outcomes are reported as mean activity minutes and daily AF%.

Results:
Comparing Pandemic vs. Pre-periods (N=82 periods; 55 male, 27 female), daily activity minutes decreased by a mean of 13.16±1.06 minutes/day, and daily AF burden increased by 16% [5%-26%]. Comparing Pre vs. Pre-Pre-Pandemic periods (N=60 periods; 41 male, 19 female), mean activity decreased by 2.28±1.13 mins/day, and AF burden increased by 57% [50%-64%]. A significant negative correlation between activity and AF burden was demonstrated (coefficient -2.0, 95% CI -2.4, -1.6). A decrease in 2.0 activity minutes was associated with a 10% increase in AF burden.

Conclusions:
This natural history analysis of PA and AF burden demonstrated decreases in activity and increases in AF burden with time and the pandemic. Activity and AF burden were significantly negatively correlated.
Abstract 4146612: The Endothelial Cell Translatome Varies by Organ and Disease Status in a Murine Heart Failure with Preserved Ejection Fraction Model
Authors: zhao debiao , Fayyaz Ahmed , Chau Sarah , Dasari Surendra , Du Aolin , Huo Yu , Redfield Margaret , Wang Ying
Published: November 2024

Background:
Dysfunction of systemic vascular endothelial cells (ECs) is common in heart failure with preserved ejection fraction (HFpEF). We sought to determine if organ-specific EC translational heterogeneity is present in HFpEF. Using a transgenic mouse model (RiboTag
EC
), we analyzed the translatome (the mRNAs bound with ribosomes) of organ-specific ECs in a mouse HFpEF model induced by hypertensive/metabolic stresses.

Methods:
Six-month-old male RiboTag
EC
(

Cdh5
CreERT2+

/

Rpl22
HA/+

) mice, expressing a hemagglutinin tag in EC ribosomal protein Rpl22, were fed a high-fat diet and L-NAME water (N=4) or a normal diet and water (N=5) for 7 weeks. Organs were collected for Translating Ribosome Affinity Purification, RNA isolation, and RNA-seq. RNA-seq data were visualized using uniform manifold approximation and projection (UMAP). Differentially expressed genes (DEGs; absolute fold change ≥ 2 and false discovery rate (FDR) adjusted p-value ≤ 0.05). Pathway enrichment analyses were conducted (Ingenuity Pathways Analysis (IPA)).

Results:
In UMAP, the EC translatome clustered by organ (heart, lung, skeletal muscle, and liver) highlighting organ-specific EC heterogeneity and by disease (HFpEF) status with cardiac ECs showing the most dramatic changes with HFpEF (Fig A). Cardiac ECs in HFpEF (vs Control) had 283 downregulated and 23 upregulated DEG (Fig B) out of 14,923 genes identified. There were significant differences in 142 canonical pathways (16 upregulated, 126 downregulated), including LXR/RXR activation, DHCR 24 signaling, regulation of insulin-like growth factors, eNOS signaling, acute phrase response (all down regulated) and IL-1b-mediated inhibition of RXR and unfolded protein response (both up regulated) (Fig C).

Conclusion:
HFpEF induction caused extensive translational changes in EC but particularly cardiac ECs. In cardiac ECs, metabolism, anti-inflammatory, vasodilation, tissue repair, and angiogenesis pathways were inhibited, while pro-inflammatory response, insulin resistance, and proteostasis pathways were activated.
Abstract 4146616: Incidence of ventricular tachycardia and fibrillation detected by an insertable cardiac monitor in a large real-world cohort of heart failure patients with reduced and preserved ejection fraction.
Authors: Kahwash Rami , Zile Michael , Khan Mohammad , Sarkar Shantanu , Van Dorn Brian , Gerritse Bart , Butler Javed
Published: November 2024

Background:
Subcutaneous insertable cardiac monitors (ICM) have the capability to detect tachycardia (tachy) which are occasionally ventricular tachycardia and fibrillation (VT/VF).

Objective:
We investigated the incidence of spontaneous VT/VF in patients (pts) implanted with an ICM and clinical history (Hx) of heart failure (HF) with reduced or preserved left ventricular ejection fraction (LVEF).

Methods:
Pts with Hx of HF admissions who were implanted with an ICM were identified from the aggregated and de-identified Optum
®
electronic health record (EHR) database during 2007-2021. The ICM collected data were merged with EHR data to create a de-identified database of real-world patients. Pts were included if they had ≥180 days of device follow-up. ICMs detect tachy if 30 of 40 recent intervals are shorter than 260 ms or if 16 consecutive intervals are shorter than tachy interval (nominally 340 ms) that is adjusted with age. Tachy episodes were first classified as VT/VF, SVT, or oversensing using an artificial intelligence (AI) model that was pre-trained using over 50K manually adjudicated ICM detected tachy episodes. If the AI model output probability for VT/VF was greater than 0.2, then those episodes were manually adjudicated for true incidence of non-induced spontaneous VT/VF. The Kaplan-Meier incidence curves for VT/VF incidence are reported as a function of reduced vs preserved ejection fraction.

Results:
A total of 1020 ICM pts with Hx of HF admission were identified from the real-world dataset. In 889 pts (87%) with available LVEF, 394 (44%) had EF<50%, and 495 (56%) had EF≥50%. In 296 pts (29%) with available NYHA class, 13%, 43%, 38%, 6% were class I, II, III, and IV respectively. Pts had an avg. age of 68±13 yrs with 52% being males and Hx of hypertension in 95%, diabetes in 56%, coronary artery disease in 75%, atrial fibrillation in 57%, stroke/TIA in 51%, and renal dysfunction in 53%. A total of 911 pts with an average follow-up of 25.8 months were included. A total of 90 tachy episodes (41 pts) were adjudicated as true VT/VF. Incidence of true VT/VF, as detected by an ICM over 36 months of follow-up, was estimated to be 5.6% with VT/VF incidence being 8.2% vs 3.8% in HF pts with reduced versus preserved LVEF (Figure).

Conclusion:
Incidence of VT/VF over 3 years of follow-up was estimated to be more than 5% in pts with ICM and Hx of HF events. VT/VF incidence was higher in HF pts with reduced versus preserved LVEF in this real-world cohort.
Abstract 4146639: Excessive Alcohol Consumption and Heart Attack Risk
Authors: Schuver Trisha , Sathiyaseelan Thiveya , Ukoha Nnenna , Annor Eugene , Obi Emeka , Karki Arpana , ahuja manik , Itopa Mercy , Osei Philomena , Nwaneki Chisom , Ghimire Achala , Neupane Hemanta , Aderinwale Oluseyi
Published: November 2024

Background:
Cardiovascular diseases are the leading cause of death globally today increasing from 14 million deaths in 2000 to 18 million deaths in 2019. Among these 85% of the deaths were from heart attacks. Excessive alcohol use is one of the preeminent preventable causes of death in the US. More than 38 million adults aged 18 and older reported binge drinking and do so on average four times a month. An increased risk of heart attack has been linked to binge drinking or heavy alcohol consumption. This study aims to study the effect of excessive alcohol consumption or binge drinking on heart attacks in the U.S.

Methods:
We used cross-sectional data from the 2022 Behavioral Risk Factor Surveillance System a nationally representative U.S. telephone-based survey of adults aged 18 years and extracted data for non-metropolitan/rural counties. Logistic regression analyses were conducted to test the association between heavy and binge drinking with lifetime reports of experiencing a heart attack. We included the following covariates and controls no health insurance, poor sleep, depression, income, race/ethnicity, educational status, and age.

Results:
Overall, 5.64% (n=445132) of the participants had heart attacks among the total study population. Neither heavy alcohol use nor binge drinking were significantly associated with experiencing a heart attack. However, age (O. R=7.480 [7.098-7.883]), male gender (O. R=2.192 [2.134-2.253], low income (O. R=1.932 [1.887-1.988]), and depression (O. R=1.445 [1.400-1.491]) were associated with a heart attack.

Conclusion:
Despite the widespread concern regarding the link between excessive alcohol consumption and heart attacks, our study found no significant association between heavy alcohol use, binge drinking, and heart attack. However, other covariates like age, male gender, low income, and depression were associated with the prevalence of heart attack which underscores the influence of social determinants of health. Further research is needed to elucidate the nuanced relationship between alcohol consumption patterns and heart health.
Abstract 4146664: Sleep duration and risk of incident heart failure in a cohort of primarily low-income Black and White adults
Authors: Full Kelsie , Xu Meng , Shi Hui , Dixon Debra , Dupuis Leonie , Gupta Deepak , Lipworth Loren
Published: November 2024

Introduction:
Short and long sleep durations have been associated with cardiovascular (CV) disease risk and mortality, but less is known about the relationship with heart failure (HF). Clinical guidelines recommend adults sleep at least 7 hours and less than 9 hours per night for optimal health. We prospectively investigated the association between sleep duration and incident HF in the Southern Community Cohort Study (SCCS), a large cohort of primarily low-income Black and White adults.

Methods:
The study included 26,669 Black and White SCCS participants without prevalent HF at enrollment (2002-2009) who were receiving Center for Medicare/Medicaid Services (CMS). Participants self-reported weekday and weekend sleep duration at enrollment; weighted average nightly sleep duration was calculated. Incident HF was ascertained using ICD-9/10 codes via CMS claims through December 31, 2016. Multivariable Cox models were conducted to test associations between sleep duration and incident HF.

Results:
Participants had a median age of 55 years, and were predominantly Black (69%), female (62%) and low-income (87% < $25,000/year). Approximately 27% of participants reported a habitual sleep duration of 8-9 hours per night, while 18%, 21%, 17% and 17% reported sleep durations <6, 6-7, 7-8 and >9 hours, respectively. Over median 10 years of follow-up, 7,375 participants (27.6%) developed HF. Compared to those who slept 8-9 hours a night, participants with a sleep duration <6 hours (HR 1.15; 95% CI 1.07-1.24) and between 6-7 (HR 1.07; 95% CI 1.00-1.15) were at greater risk for incident HF independent of demographics, socioeconomic indicators, employment, and health behaviors including smoking, alcohol consumption, physical activity, and diet (
Figure 1
). The association for the shortest sleep duration (<6 hours) persisted after adjustment for CV risk factors and depressive symptoms (HR 1.10; 95% CI 1.02-1.18). Sleep durations ≥9 hours were not significantly associated with HF risk.

Conclusions:
Shorter sleep duration was associated with higher risk of developing HF in a cohort of middle aged Black and White adults. Strategies to promote optimal sleep duration may improve primary prevention of HF among individuals at high-risk.
Abstract 4146665: Unveiling the Biological Subtypes of Left Ventricular Diastolic Dysfunction through Unsupervised Clustering of ECG Data
Authors: Shetty Samantha , Lampert Joshua , Jiang Joy , Nadkarni Girish , Vaid Akhil
Published: November 2024

Left Ventricular Diastolic Dysfunction (LVDD) presents a challenge in terms of management given its multifaceted etiology and complex presentation. Conventional diagnostic categories may fail to fully reflect underlying pathophysiology variability. Using unsupervised clustering on electrocardiogram (ECG) data is a novel approach to capture subtle changes in the electrical signatures seen in ECGs and help uncover naturally occurring patient subtypes that may be invisible to traditional echocardiographic (echo) assessment.

We performed Natural Language Processing on long-form echo reports to extract annotations of LVDD. Echo reports were paired with an ECG performed within 7 days of the echo. Patients were excluded if their ECG diagnostic codes indicated conduction abnormalities, concurrent ischemia, and prior intervention. We applied a Convolutional Autoencoder to compress high-dimensional ECG data into a 128-dimensional, feature-rich space suitable for clustering. K-means clustering was then utilized to categorize patients into groups based on transformed ECG features. Silhouette analysis was employed to determine the optimal number of clusters and quantify differences between groups. Chi-square and ANOVA tests examined for differences in age, sex, and race across clusters.

We identified 22,183 patients paired with 96,921 ECGs with clinician confirmed LVDD. Silhouette score analysis on K-Means clustering identified 2 as the optimal number of clusters (Figure 1). Labels associated with each data point were visualized in 2D and 3D projections with the t-Stochastic Neighbor Embedding technique (Figure 2). Identified clusters differed significantly in terms of age, sex, and race, with p-values of <0.00001 for each demographic.

The identification of two distinct clusters underscores the potential of ECG-based phenotyping in revealing new biological subtypes of LVDD. Extending this technique to integrate other clinical variables and longitudinal data may enhance the clinical utility of identified subtypes. Future work will look at cluster-wise distribution of co-morbidities and longitudinal outcomes. Applying similar methodologies to other cardiac disorders may improve our approach to their diagnosis and management. Employing unsupervised clustering on ECG has proven to be effective in identifying novel subtypes of LVDD, showcasing the potential of ECG data to refine diagnostic and therapeutic strategies.
Abstract 4146666: The Risk of Bundle Branch Block Following Transcatheter Aortic Valve Implantation Across Different Valve Types: A Systematic Review with Meta-Analysis
Authors: Abdulelah Zaid , Abdulelah Ahmed , Al-Dqour Mohammad , Rommaneh Muna , Salah Qais , Al Daradkah Jude , Alhajahjeh Abdulrahman , Al Balbissi Kais
Published: November 2024

Introduction:
Transcatheter aortic valve implantation (TAVI) is widely regarded as the treatment modality of choice for the effective and safe treatment of native aortic stenosis among patients with high surgical risk. However, bundle branch block (BBB) following TAVI is well-documented and widely regarded to be the leading complication associated with TAVI, along with other conduction abnormalities such as atrioventricular node block (AVB).

Research Question:
is the risk of BBB higher with a particular type of TAVI valve compared to the rest?

Aim:
To evaluate the risk of developing BBB following TAVI across the different valve types in a systematic and meta-analytic approach.

Methods:
The following databases were searched; PubMed, Scopus, Cochrane Library, and ClinicalTrials.gov. We used the following keywords in the search; ((Transcatheter aortic valve implantation OR Transcatheter aortic valve replacement OR TAVI) AND (Bundle branch block OR Right bundle branch block OR Left bundle branch block OR BBB)). The studies were included if they reported the prevalence of BBB in patients undergoing TAVI with a specified type of valve such as balloon-expandable valve (BEV), self-expandable valve (SEV), and mechanical-expandable valve (MEV).

Results:
A total of 827 articles were initially identified and eventually only 176 studies were thoroughly reviewed. Finally, 105 articles (55 BEV, 44 SEV and 6 MEV) were included in this systematic review and meta-analysis with a total number of included patients being 65,491. The prevalence of patients who underwent BEV and developed a bundle branch block were 30% (95%CI 0.29-0.31). Moreover, the prevalence of bundle branch block in patients who had a SEV implant were 16% (95% CI 0.16-0.16), whereas patients who underwent a MEV implant had an exceptionally high prevalence of bundle branch block of 54% (95%CI 0.52-0.56). The overall prevalence of BBB in patients undergoing a TAVI was 31% (95% CI 0.17-0.50) using random effects model. Utilization of this model also demonstrated significant heterogeneity (P-value<0.001, I2=100%)

Conclusion:
The prevalence of bundle branch block following TAVI is alarmingly high at an overall rate of 31%. More importantly, MEV implants demonstrated a worrisome 54% overall prevalence of bundle branch block, and thus hindering their potential utilization, especially among patients with pre-existing bundle branch block.
Abstract 4146680: Detecting Atrial and Ventricular Ectopy from the Apple Watch with an novel Deep Learning algorithm
Authors: Kennedy Alan , Doggart Peter , Albert David
Published: November 2024

Introduction:
Personal electrocardiogram (ECG) devices have significant potential for monitoring abnormal heart rhythms outside clinical environments. However, the reliability of these devices heavily depends on their automated ECG analysis capabilities, which guide patients on whether medical consultation is necessary. Many consumer-grade devices, such as the Apple Watch ECG (AW-ECG), frequently classify atrial and ventricular ectopy as ‘inconclusive’.

Hypothesis/Objective:
To evaluate the performance of a novel deep learning algorithm in detecting atrial fibrillation (AF), premature ventricular contractions (PVCs), and premature atrial contractions (PACs) from AW-ECG recordings.

Method:
A database of 2,500 AW-ECG recordings was analysed, each annotated by four electrophysiologists, with a consensus annotation used as the ground truth. The algorithm's performance in detecting AF, PVC, and PAC was assessed by measuring sensitivity, specificity, and positive predictive value (PPV) against the electrophysiologists' consensus.

Results:
For AF detection, the AI algorithm achieved a sensitivity of 94% (95% CI: 90, 96), specificity of 99% (95% CI: 99, 100), and PPV of 94% (95% CI: 90, 96). For PVC detection, the sensitivity was 84% (95% CI: 79, 88), specificity was 99% (95% CI: 99, 100), and PPV was 91% (95% CI: 87, 94). For PAC detection, the sensitivity was 71% (95% CI: 65, 77), specificity was 97% (95% CI: 97, 98), and PPV was 75% (95% CI: 69, 80).

Conclusion:
The study highlights the potential of a novel AI algorithm to accurately detect AF, PVCs, and PACs from AW-ECG recordings. The integration of this algorithm into AW-ECG analysis could significantly improve the identification of atrial fibrillation and ectopic beats, thereby reducing the frequency of inconclusive interpretations and minimising the need for human review.
Abstract 4146681: Effect of Sacubitril/Valsartan on the Right Ventricle after High-Risk Myocardial Infarction: Insights from the PARADISE-MI Trial
Authors: Wang Xiaowen , Shah Amil , Claggett Brian , Karimi Taheri Kimia , Jering Karola , Kovacs Attila , Merkely Bela , Nagy Vivien , Cikes Maja , Rouleau Jean , Pfeffer Marc , Solomon Scott
Published: November 2024

Background:
Right ventricular (RV) dysfunction is a common complication after myocardial infarction (MI) and a risk factor for adverse events. Effect of sacubitril/valsartan (S/V) on RV function in patients after MI is unknown.

Hypothesis:
RV dysfunction is associated with adverse events following high-risk MI and treatment with S/V attenuates adverse RV remodeling and functional impairments in high-risk post-MI patients.

Aims:
To compare the baseline clinical and echocardiographic parameters by quartiles of RV fractional area change (RVFAC), and to evaluate the effect of S/V (compared to ramipril) on RV size and function from randomization to 8 months in post-MI patients with LVEF≤40% and/or pulmonary congestion.

Methods:
Among the 5,661 participants in PARADISE-MI trial, 544 were enrolled in the echocardiographic sub-study. Baseline characteristics were assessed across quartiles of RVFAC (N=446). Cox proportional hazards model was used to assess the association between RVFAC and clinical outcomes. Treatment effects of S/V compared to ramipril on were assessed using linear regression. The primary outcome was cardiovascular (CV) death or incident HF (defined as HF hospitalization or outpatient symptomatic HF).

Results:
Baseline clinical characteristics were similar across quartiles of RVFAC, with the exception that patients with higher RVFAC were more likely to be female (Table 1). Higher RVFAC was associated with higher LVEF, smaller LV chamber size, and lower E/e’ ratios (Table 1). A lower baseline RVFAC was associated with a higher risk of incident HF, but not associated with a higher risk of primary outcome or CV death (Figure 1). Changes of RVFAC, RV end-diastolic area, RV end-systolic area, tricuspid annular S’, and RV outflow tract velocity-time integral from randomization to 8 months were similar in those randomized to S/V compared to ramipril. Baseline RVFAC did not modify the treatment effect of S/V on RV size or RVFAC (p-interaction > 0.16).

Conclusion:
In high-risk post-MI patients, a lower RVFAC was associated with worse LV systolic and diastolic function and higher risk of incident HF. Compared to ramipril, S/V was not superior in improving RV systolic function.
Abstract 4146687: Hemodynamic Impacts of Central Arterial Stiffness and Coronary Flow Reserve on LV filling Impairment in Patients With Normal Left Ventricular Systolic Function
Authors: CHANG YOUNING , Sung Shih-Hsien
Published: November 2024

Background:
Heart failure with preserved left ventricular ejection fraction (LVEF) prevails in subjects who complained of exercise intolerance, which is characterized by elevated left ventricular filling pressure (LVFP). While arterial stiffness has been related to left ventricular diastolic dysfunction, little is known whether the coronary flow reserve mediates the association. The invasive study then investigated the correlations between arterial stiffness, coronary flow reserve and LVFP.

Methods:
Subjects, referred for coronary angiography were eligible for this study and patients with stenotic lesions coronary artery disease (CAD) over 70% in any of which coronary vessels were excluded. Pressure waveforms of right radial artery (RRA), ascending aorta, and left ventricle were obtained, and left ventricular end-diastolic pressure (LVEDP) were measured. Aortic augmentation index (AI), aorto-radial pulse wave velocity (arPWV), and left ventricular diastolic time constant (Tau) were calculated. Three-dimensional quantitative coronary angiography (3D-QCA)-based vessel FFR (vFFR) of each coronary artery were measured. Increased LVFP was defined as LVEDP ≥ 20mmHg.

Results:
Among a total of 244 participants, 152 subjects had increased LVFP. While the demographic data, morbidities, hemogram, biochemistries, blood pressure, FFR, and LVEF were almost similar between groups, subjects with increased LVFP had higher RRA AI, aortic AI, subendocardial viability ratio, and Tau. Stepwise regression showed subendocardial viability ratio and Tau played the crucial role while increased LVFP. Correlation matrix analysis showed aortic AI, Tau, and RRA AI and all three vessels vFFR correlated with LVEDP. The multiple logistic regression analysis demonstrated positive correlation between radial AI, and Tau but inversely correlation between subendocardial viability ratio and no correlation between three vessels vFFR with increased LVFP.

Conclusions:
Among subjects with CAD but no stenotic lesions over 70% among three vessels, aortic stiffness was associated with elevated LVFP, suggesting some hemodynamic impacts of central arterial stiffness on LV filling impairment patients with normal left ventricular systolic function. About coronary flow reserve and other diastolic indices, represented with vFFR and subendocardial viability ratio and Tau, respectively, the discordance results among correlation matrix and logistic regression analysis needs further studies to investigate.
Abstract 4146699: Blunted Hemodynamic Reactivity to Acute Mental Stress in the Lab is Associated with Autonomic Inflexibility at Home
Authors: Shah Amit , She Hua , elon lisa , Roberts Tatum , Stefanos Lewam , Haddad George , Osei Jeffery , Suvada Kara , Okoh Alexis , Desai Shivang , Gold Matthew , Jain Vardhmaan , Yadalam Adithya , Razavi Alexander , Wiltshire Charis , Raggi Paolo , Pearce Brad , Quyyumi Arshed , Sameni Reza , Bremner J Douglas , Clifford Gari , Vaccarino Viola
Published: November 2024

Background:
Growing evidence suggests that blunted blood pressure and heart rate responses to acute psychological stress independently associate with an increased risk of adverse outcomes in individuals with CHD, but assessment of mental stress reactivity in clinical settings is resource intensive. An alternative approach is to passively measure stress physiology at home with wearables, which is easier to translate into clinical practice. We tested the hypothesis that blunted mental-stress hemodynamic reactivity in the lab is associated with digital biomarkers of autonomic inflexibility at home.

Methods:
We conducted a mental stress test in 239 participants (age < 60 years) with an MI within 8 months. Participants underwent a speech stressor task in front of an audience to induce mental stress, during which blood pressure and heart rate were measured repeatedly during a baseline 15-minute rest period and 5-minute stress challenge. Participants went home with a 7-day Holter monitor to measure autonomic function. We examined vagal autonomic inflexibility with deceleration capacity (DC), a digital biomarker calculated via phase rectified signal averaging of heart rate intervals. We also examined low frequency (LF) heart rate variability (HRV), an indirect measure of baroreceptor sensitivity. We measured mean values from 5-minute windows during sedentary periods only to avoid confounding due to physical activity. We used multivariable linear regression models to adjust for potential confounding due to age, beta-blockers, and sex.

Results:
The mean age was 52 years, 51% were black, and 36% were women. Lower DC most strongly associated with a blunted change in heart rate during acute mental stress challenge (adjusted p<0.0001), followed by rate pressure product (p=0.01), systolic blood pressure (p=0.02), and diastolic blood pressure (p=0.035). The results were similar for LF HRV. We also found that the relationship was stronger in women than in men, especially for heart rate changes with stress and LF HRV (figure). Each 10 BPM reduction in heart rate reactivity associated with a 14% and 7% reduced DC in women and men, respectively. Corresponding reductions for LF HRV were 30% and 13% (p<0.05 for all).

Conclusions:
In young and middle-aged individuals with recent MI, laboratory-induced hemodynamic changes with stress associate with digital biomarkers of autonomic inflexibility during sedentary periods, especially in women.
Abstract 4146800: A Retrospective Analysis of Measured Versus Estimated Resting Oxygen Uptake for Derivation of Fick Cardiac Output in Patients in the Cardiac Intensive Care Unit
Authors: Minasian Alexandra , McGinnis Shaina , Rouvina Jennifer , Newlands Chloe , Griskowitz Catharine , Kowal Alyssa , Kelly Katherine , OLoughlin Joseph , Wallace DayQuan , Dudzinski David , Shelton Ken , Malhotra Rajeev , Lewis Gregory
Published: November 2024

Background:
Estimated cardiac output using the Fick principal (estFickCO) frequently informs clinical decision making in Cardiology Intensive Care Units (CICU). Assessment of estFickCO relies on estimation of resting oxygen uptake (rVO
2
). We hypothesized that large variance will be present between rVO
2
measured with a metabolic cart and the estimated rVO2 often used in CICUs.

Methods:
In this single-center study, 275 CICU patients with pulmonary arterial catheters in place to guide heart failure management underwent breath-by-breath metabolic cart measurement of rVO
2
for 10 minutes coupled with duplicate measures of arterio-venous oxygen content to derive Fick CO. Four equations to estimate rVO
2
were evaluated: weight-based only (3.5ml/kg/min, 1 MET); accounting for sex and BSA (Dehmer); sex, BSA, and age (Bergstra); and sex, BSA, age, and heart rate (LeFarge). Bland-Altman analysis and derivation of coefficients of variation were performed to evaluate the agreement between each equation and actual measured rVO
2
.

Results:
In this cohort of 275 patients (age 57.8±14.4, 24% female, BMI 28±6.9 kg/m
2
) the mean measured rVO
2
was 276±71 mL/min and Fick CO was 4.7±1.6 L/min. Using 1 MET to estimate rVO
2
equated to a mean rVO
2
of 292±81 mL/min, the Dehmer equation estimated a mean rVO
2
of 283±49 mL/min, Bergstra estimated a mean rVO
2
of 248±37 mL/min, and the LaFarge equation estimated a mean rVO
2
of 239±53 mL/min. The frequency of error being >25% was calculated at 24%, 15%, 17%, and 19% respective to each equation. When analyzed using Bland-Altman plots, the Dehmer equation demonstrated the lowest mean bias as well as the lowest coefficient of variation when compared to the other three estimates (
Figure
) yet limits of agreement span VO
2
values associated with > 3 L/min differences in Fick CO across all 4 estimates.

Conclusion:
Measured VO
2
varies significantly from estimated VO
2
among CICU patients. Accounting for sex and BSA with use of the Dehmer equation was associated with the closest approximation of actual VO
2
values among 4 estimates analyzed in our study. High variance in rVO
2
estimates and impacts on management should be considered when interpreting estFickCO in CICU patients.
Abstract 4146808: Evaluating the Impact of Simulation Training on Transesophageal Echocardiography Proficiency in Fellows: An Updated Meta-Analysis of Randomized Controlled Trials
Authors: Fukunaga Christian , Katsuyama Eric , Prata Alonzo , Fernandes Julia , Coan Ana Carolina , Petri Santos Pinheiro Rafael , Falco Neto Wilson , Scardini Pedro Gabriel , Andrade Naieli , Gioli-Pereira Luciana
Published: November 2024

Introduction:
Simulation-based training systems for Transesophageal Echocardiography (TEE) have been developed for medical education, but evidence on their effectiveness remains limited. This study aimed to evaluate the efficacy of simulation-based teaching compared to traditional methods in imparting TEE knowledge and skills to fellows.

Methods:
A literature search was conducted across MEDLINE, Embase, and Cochrane databases. The primary endpoint was (1) post-intervention skill or knowledge assessment. A subgroup analysis was performed comparing anesthesiology and cardiology fellows. Additionally, a secondary single-arm analysis evaluated (2) the recommendation rate for simulation training among participants who underwent this form of tutoring. Statistical analysis was done using R Studio 4.3.2.

Results:
We included 9 RCTs encompassing 602 fellows, of whom 293 (48.67%) underwent simulation training TEE with a mean age of 25. In the pooled analysis, the simulation group's post-test scores for TEE proficiency were significantly higher compared to the control group (SMD: 0.86; 95% [CI] 0.48-1.24; p < 0.01; Figure 1A). Our subgroup analysis showed no significant difference between anesthesiology and cardiology fellows (p=0.36; Figure 1B). The Likert recommendation score indicated a high recommendation rate of 92% (95% CI 0.75-1.00; Figure 2) for the simulation education group.

Conclusion:
In this updated meta-analysis, fellows who underwent simulation training for TEE achieved higher post-assessment scores, and the Likert recommendation rate for simulation-based teaching was high. Additionally, there were no significant subgroup differences between the cardiology and anesthesiology fellows.
Abstract 4146844: Characterization of Novel Cardiovascular Medication Use by Clinical Specialty After Admission for Heart Failure or Coronary Artery Disease
Authors: Salahuddin Taufiq , Chow Christine , Hebbe Annika , Simons Carol , Helfrich Christian , Doll Jacob
Published: November 2024

Background:
Angiotensin receptor-neprilysin inhibitors (ARNI), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP-1 RA) have well-established benefit for patients with heart failure (HF) or coronary artery disease with type 2 diabetes (CAD+T2D), but use remains low. We aimed to characterize post-hospitalization use of these novel medications by provider specialty in the Veterans Health Administration (VA).

Methods:
Using VA health record and administrative data, two patient cohorts were retrospectively identified with hospitalization from 2017-2023 for either HF or CAD+T2D. Provider-level encounter data and outpatient prescriptions within 6 months of discharge were assessed for ARNI and SGLT2i for HF and SGTL2i or GLP-1 RA for CAD+T2D among primary care, cardiology, endocrinology, and nephrology providers. Medication utilization was counted equally for providers seeing the same patient, regardless of which provider initiated the prescription. Descriptive statistics were used to characterize frequency and proportions of novel medication use by specialty in 4 categories with respect to hospital discharge: 1) only before, 2) continued, 3) new start, or 4) untreated.

Results:
There were 215,816 patient-provider encounters in the HF cohort and 171,540 encounters in the CAD+T2D cohort. Cardiology providers had the highest rate (11.9%) and largest number (n=11,397) of new starts for ARNI. For SGLT2i for HF, endocrinology had the highest rate (12.9%) but the smallest number (n=794) of new starts. For SGTL2i or GLP-1 RA for CAD+T2D, endocrinology had the highest rate (13.8%), but primary care had the highest number (n=7,426) of new starts. In total, 10% of visits had a new start while >70% of patients were untreated with novel medication classes.

Conclusion:
Most post-hospitalization care for HF and CAD+T2D was provided by primary care and cardiology. Cardiologists and endocrinologists were most likely to use novel cardiovascular medications, but endocrinologists accounted for a small proportion of total HF and CAD care. Future work should focus on implementation strategies to address the large opportunity for improvement in guideline-concordant care across all specialties.
Abstract 4146856: Aberrant Regulation of endMT in Turner Syndrome: Implications for the Pathogenesis of Congenital Cardiovascular Disease
Authors: Garcia Huitron Eric Ivan , Zhang Xiaoying , Babcock Lance , Grande-Allen Kathryn , Prakash Siddharth
Published: November 2024

Introduction:
Turner syndrome (TS) is caused by the partial or complete absence of one sex chromosome and affects 1 in 2500 liveborn infants. Hypertension, bicuspid aortic valve, and thoracic aortic aneurysms are more prevalent in TS compared to the general population. We hypothesize that persistent abnormalities of endothelial-mesenchymal transition (endMT) in the embryo and adult mediated in part by abnormal responses to shear stress predispose to cardiovascular disease in TS. The objective of this study was to define functional and transcriptomic differences between euploid 46,XX and aneuploid 45,X induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) from adult donors with mosaic TS.

Methods:
iPSCs were reprogrammed from peripheral blood mononuclear cells. Individual colonies were genotyped to identify isogenic euploid and aneuploid iPSC subclones, which were differentiated into ECs using standard methods. After selection for CD31 expression, baseline EC properties and response of EC monolayers to shear stress using a cone and plate viscometer system were characterized using fluorescence microscopy, qPCR, RNA sequencing, and functional assays.

Results:
We generated 45,X, 46,X,iso(X)(q10) [iso], and 46,XX iPSCs from one mosaic donor. After confirming genomic integrity and pluripotency, we successfully differentiated multiple iPSC subclones of each karyotype into ECs. EC morphology, tube formation, and uptake of DiI-conjugated acetylated low-density lipoproteins were not significantly different between subclones, although 45,X ECs proliferated more slowly than 46,XX or iso ECs. Collagen gel contraction and migration by 45,X ECs was significantly higher than 46,XX or iso ECs at baseline and in response to exogenous TGF-β peptide. Comparative RNAseq and qRT-PCR analysis of 45,X and 46,XX ECs showed that
VCAM1
,
SNAI1
,
ACTA2, TWIST1
, and other endMT-associated genes were significantly upregulated at baseline in 45,X ECs and were only partially suppressed by shear stress, while expression of
CDH2
was decreased in 45,X ECs. We also observed that 45,X ECs but not 46,XX or iso ECs underwent spontaneous endMT in static culture conditions.

Conclusion:
Despite similar baseline EC phenotypes, the threshold for endMT activation appears to be lower in 45,X ECs compared to 46,XX or iso ECs. Dysregulation of endMT, possibly due to chronic derepression of
SNAI1
expression, may contribute to congenital cardiovascular disease in TS.
Abstract 4146863: Efficacy of Hydralazine-Isosorbide-Dinitrate and Sodium-glucose Cotransporter-2 Inhibitors in Reducing Short-Term Readmission in African Americans with Advanced Heart Failure
Authors: Kluever Mark , Javeed Masi
Published: November 2024

Introduction:
The treatment of heart failure (HF) with hydralazine-isosorbide dinitrate (H-ISDN) in African Americans (AA) with New York Heart Association (NYHA) III-IV who remain symptomatic despite optimal medical therapy is a class Ia indication. However, the efficacy of guideline directed medical therapy (GDMT) which combines sodium-glucose cotransporter-2 inhibitors (SGLT2i) and H-ISDN in reducing hospital readmissions has not been well studied.

Hypothesis:
In self-identified AA adults with advanced heart failure on GDMT including hydralazine-isosorbide dinitrate, the use of a SGLT2i reduces hospitalization for HF.

Methods:
The patients studied were self-identified AA with advanced HF on GDMT [including any dose of an angiotensin receptor-neprilysin inhibitor (ARNi) or an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB), a mineralocorticoid receptor antagonist (MRA), a beta-blocker (BB), H-ISDN, with or without treatment with an SGLT2i]. Data was obtained from the Hospital Corporation of America (HCA) enterprise-wide database from January 2020 to September 2023 using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). The final cohort was divided into two groups: Group 1 consisted of those treated with an ARNi/ACEi/ARB, MRA, a beta blocker, and H-ISDN while Group 2 included those receiving the same combination of medications with the addition of an SGLT2i. Differences in baseline characteristics were analyzed between the two groups. Logistic regression was used to analyze the relationship between the treatment groups and hospital readmission within 90 days.

Results:
Only 517 AA met inclusion criteria and did not meet exclusion criteria, which included a history of valvular heart disease, hypertrophic or restrictive cardiomyopathy, active myocarditis, history of cardiac arrest, and life-threatening arrhythmias. When controlling for age, gender, diabetes, chronic kidney disease, atrial fibrillation, body mass index, and smoking status, there was no significant difference in the likelihood of 90-day hospital readmission between patients whose GDMT with H-ISDN included an SGLT2i and those whose treatment did not.

Conclusions:
The results suggest the incorporation of an SGLT2i into GDMT with H-ISDN in AA with advanced HF does not confer additional benefits in the reduction of short-term hospital readmissions for heart failure.
Abstract 4147016: Trends in Hypertension-related End-Stage Renal Disease (ESRD) across the United States from 1999-2022: An Analysis of Age, Gender, and Ethnic Disparities
Authors: Ayyan Muhammad , Amir Saim , Zahid Afra , Naveed Aiman , Umer Mohammad , Siddique Muhammad Uzair , Rehman Wajeeh , Dani Sourbha
Published: November 2024

Introduction:
One of the main causes of renal disease, in which the kidneys are unable to function properly, is hypertension. Over time, uncontrolled hypertension can harm the fragile blood vessels in the kidneys, resulting in chronic kidney disease (CKD) and eventually end-stage renal disease (ESRD). In this study, we examined the trends of hypertension-related ESRD mortality in the United States from 1999 to 2022 and determined the disparities between various epidemiological groups.

Methods:
Our study conducted an in-depth search of the Centers for Disease Control and Prevention’s Wide- Ranging Online Data for Epidemiological Research (CDC Wonder) database and retrieved data on hypertension-related end-stage renal disease mortality from 1999 to 2022. Age-adjusted mortality rates (AAMR) per 100,000 individuals and associated annual percent changes (APC) for the overall study population were calculated using Joinpoint Regression Analysis. The data was further stratified into epidemiological groups of age, gender, ethnicity, and census region.

Results:
A total of 938,095 deaths occurred from hypertension-related end-stage renal disease. It was observed that the overall AAMR for hypertension-related ESRD increased from 1999-2022 with a fixed APC of 9.08. The populations with the highest mortality rates were males, African Americans, non-Hispanics, and the age group of over 85 years. Region-wise analysis gave variable trends in the AAMR (Overall APC: Northeast: 8.42, Midwest: 10.29, West: 9.04, and South: 12.80 from 2011-2022).

Conclusion:
In the US, the mortality rates from hypertension-related ESRD have shown a constant incline. The need for additional research and action is highlighted by persistent differences in mortality that are related to geography and demographics.