bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18211: Does Frailty Matter in High Risk PCI
Authors: Kochar Ajar , Peterson Benjamin , Young Rebecca , Nanna Michael , Rymer Jennifer A , Damluji Abdulla , Alexander Karen P , Senman Balimkiz , Sutton Nadia R , Orkaby Ariela , Bhatt Deepak
Published: December 2023

Background:
There are limited data depicting the relationship between frailty and in-hospital outcomes for high-risk PCI.

Methods:
The Cath-PCI registry (2018 - 2020) was used to examine the association of frailty as defined by the Canadian Study of Health and Aging (CSHA) frailty index and in-hospital complications for patients undergoing PCI. We conducted a logistic regression analysis for in-hospital mortality.

Results:
The sample size was 1,316,390 individuals aged ≥ 65 years undergoing PCI. The frailty distribution was: 78,921 not frail (6.0%), 892,695 pre-frail (67.8%), 284,444 frail (21.6%), and 60,330 severely frail (2.2%). The median age of patients who were frail was 76 years, 39.4% were female, and 87.2% were white. In-hospital rates for any bleeding stratified by frailty status were: not frail: 1.0%, pre-frail: 1.5%, frail 3.3%, severely frail 8.9%. The adjusted odds ratio (aOR) regarding in-hospital mortality among PCI patients at high bedside mortality risk for pre-frail, 2.58 (95% CI: 1.42 - 1.80) for frail, and 5.14 (95% CI: 4.56 - 5.80) for severely frail. The adjusted association for in-hospital mortality across sub-groups stratified by frailty status was: left main PCI ~ pre-frail aOR 1.44 (95% CI: 1.01 - 2.05), frail aOR 2.18 (95% CI: 1.53 - 3.11) and severely frail aOR 3.98 (95% CI: 2.79 - 5.70). While the aORs for chronic total occlusion were ~ pre-frail 1.57 (95% CI: 0.97 - 2.52), frail 2.31 (95% CI: 1.43 - 3.75) and severely frail 6.04 (5.40 - 6.75) and cardiogenic shock ~ pre-frail 1.33 (95% CI: 1.08 - 1.64), frail 1.54 (95% CI: 1.25 - 1.90) and severely frail 2.44 (1.99 - 3.00).

Conclusions:
Contemporary PCI is commonly performed on frail patients. Frailty is associated with higher risk of mortality across high-risk PCI categories; however, severe frailty depicts a distinct and exceptionally high-risk cohort.
Abstract 18221: Interleukin-6 in Patients With HFrEF and the Effect of Dapagliflozin: Insights From DAPA-HF
Authors: Docherty Kieran , Welsh Paul , Anand Inder S , Berg David , de Boer Rudolf A , Kober Lars , Kosiborod Mikhail N , Martinez Felipe , OMeara Eileen , Morrow David , Petrie Mark , Ponikowski Piotr , Sabatine Marc S , Schou Morten , Sattar Naveed , Hammarstedt Ann , Langkilde Anna Maria , Sjostrand Mikaela , Solomon Scott , Jhund Pardeep S , McMurray John J
Published: December 2023

Introduction:
Inflammation plays an important pathophysiological role in the development and progression of heart failure (HF). Interleukin-6 (IL-6) is a circulating cytokine which is the main regulator of the release of C-reactive protein (CRP) along with pro-inflammatory cytokines. It has been suggested that one of the potential mechanisms of action of sodium glucose co-transporter 2 (SGLT2) inhibitors may be to reduce inflammation. We examined the association between IL-6 and outcomes in patients with HF with reduced ejection fraction (HFrEF) in the DAPA-HF trial and its relationship with the effect of dapagliflozin.

Methods:
Key inclusion criteria were: 1) NYHA class II-IV, 2) LVEF ≤40%, 3) elevated NT-proBNP and 4) eGFR ≥30 ml/min/1.73m
2
. The primary outcome was a composite of a first episode of worsening HF or cardiovascular death. IL-6 (Roche Diagnostics, e411) was measured at baseline and 52 weeks.

Results:
Median (IQR) baseline IL-6 was 6.01 pg/mL (interquartile range 4.18-9.29) in the 2980/4774 with available data. Baseline IL-6 quartiles were: Q1 ≤4.18 pg/mL, Q2 4.19-6.01 pg/mL, Q3 16.02-9.29 pg/mL, Q4 ≥9.3 pg/mL. Median high-sensitivity CRP at baseline was 1.13 mg/L and 3.78 mg/L in those with an IL-6 level < or ≥ the median, respectively. The adjusted risk of the primary outcome relative to Q1 was: Q2 = HR 1.39 (95%CI 1.02, 1.89), Q3 = HR 1.55 (1.15, 2.08), Q4 = 2.07 (1.55, 2.76) (
Fig A
). The beneficial effect of dapagliflozin compared with placebo was consistent whether IL-6 was analysed in quartiles (P
int
= 0.77) or as a continuous variable (P
int
= 0.69 [
Fig B
]). The placebo-corrected relative change in IL-6 at 52 weeks was -4.1% (95%CI -9.1, +1.2), p=0.13.

Conclusions:
In DAPA-HF, elevated IL-6 levels were an independent predictor of the risk of cardiovascular death or worsening HF. Dapagliflozin reduced the risk of cardiovascular death or worsening HF regardless of baseline IL-6.
Abstract 18244: A Multi-Ancestry GWAS of Calcific Aortic Stenosis Among 2.7 Million Individuals
Authors: Small Aeron M , Dufresne Line , Farber-Eger Eric , Abner Erik , Corey Kristin , Stefánsson Kári , Nadauld Lincoln , Bundgaard Henning , Lee Jiwoo , Schumacher Johannes , Trenkwalder Teresa , Soderberg Stefan , Ganna Andrea , Rader Daniel J , Moksnes Marta Riise , Lin Meng , Laporte Fabien , Larsson Susanna , Smith Gustav , Do Ron , Ito Kaoru , Holm Hilma , Sun Yan , Kim Kelly , WILSON PETER , Odonnell Christopher J , Peloso Gina , Engert Jamie C , Thanassoulis George , Natarajan Pradeep
Published: December 2023

Introduction:
Calcific aortic stenosis (CAS) is a common, progressive fibrocalcific pathology of the aortic valve without medical therapy. The genetics of CAS remain only partially understood.

Methods:
We performed a genome wide association study (GWAS) of CAS among 2,799,598 individuals from the International Aortic Valve Genetics Consortium (IAVGC), comprising 28 cohorts. CAS was identified using a common ICD/CPT based phenotype. GWAS were meta-analyzed using inverse variance weighting with adjustment by linkage-disequilibrium score regression (LDSR) intercept. Unique genome-wide significant (GWS) loci and causal genes were annotated by nearest gene and eQTL colocalization. Genetic correlations were performed against atherosclerotic, adiposity, and lipid traits using LDSR with publicly available GWAS (CARDIoGRAMplusC4D for coronary artery disease [CAD], Million Veteran Program for peripheral artery disease [PAD], MEGASTROKE for ischemic stroke [IS], GIANT for body mass index [BMI], and GLGC for lipids).

Results:
There were 85,329 individuals with CAS (79,397 White, 3,126 Black, 1,403 Hispanic, and 1,403 East Asian) among 2,799,598 individuals. Meta-analysis of GWAS resulted in 224 unique GWS genomic regions, of which 205 were novel. The majority of the GWS genomic regions (134) did not overlap with prior risk loci for CAD, PAD, IS, BMI, or lipids. Genetic correlation demonstrated modest but significant correlations between CAS and CAD (
r
=0.26, p=3.3x10
-18
), PAD (
r
=0.41, p=1.4x10
-30
), IS (
r
=0.18,p=2.8x10
-7
), BMI (
r
=0.22,p=8.6x10
-30
), and lipids (LDL-C
r
=0.17,p=3.6x10
-10
;triglycerides
r
=0.10,p=1.9x10
-5
; HDL-C
r
=-0.07,p=8.0x10
-4
).

Conclusions:
This largest to-date multi-ancestry GWAS of CAS identified 205 novel genomic regions. We demonstrate that CAS is genetically distinct from cardiometabolic traits, with only modest genetic correlations and with a majority of CAS risk loci having no overlap with cardiometabolic GWAS risk loci.
Abstract 18249: Artificial Intelligence-Based Electrocardiogram Prediction for Duration of Atrial Fibrillation
Authors: Park Youngjun , Kim Kyung Geun , Joo Sunghoon , Chang Mineok , Lee Yeha
Published: December 2023

Introduction:
Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with poor clinical outcomes, including stroke, acute coronary events, and heart failure. Recent studies have shown that early rhythm treatment of new-onset atrial fibrillation improves the patient's prognosis. However, atrial fibrillation is often asymptomatic, and it is difficult to determine its duration accurately. Recently, AI-based ECG has been studied for various cardiovascular diseases.

Hypothesis:
We sought to develop and validate a predictive model of the ECG for the duration of atrial fibrillation
.

Methods:
All patients aged 18 years older from the two hospitals with at least one ECG were included in the study. Only patients with sinus rhythm with ECG prior to atrial fibrillation with ECG were selected. An ECG within 1 year from AF was first documented in ECG was defined as new onset AF. After dividing our datasets into training (and test sets, we developed an end-to-end deep neural network to predict for the duration of AF. Performance evaluation was conducted using various metrics, including AUROC, AUPRC, sensitivity, specificity, F1 score.

Results:
The dataset consisted of 83,525 ECGs from 16,193 patients from two hospitals. The AUROC for discriminating old AF and new-onset AF is 0.8186 (0.8181 - 0.8190) on internal validation set and 0.7967 (0.7966 - 0.7969) on external validation set. Sensitivity, Specificity, and F1 score are 0.7126((0.7118-0.7134), 0.7697 (0.7693-0.7701) and 0.5751 (0.5745-0.5757) on internal validation set and 0.7309 (0.7307-0.7311), 0.7225 (0.7224-0.7227) and 0.6354 (0.6352-0.6356)on external validation set.

Conclusions:
Our deep learning model can be used to predict atrial fibrillation's duration. Additional studies are ongoing to understand the relative importance of ECG features.
Abstract 18268: Angina and Functional Capacity Among Women Presenting With Angina and Non-Obstructive Coronary Disease
Authors: Roca Alvarez Yulith , Ashokprabhu Namrita , Bartone Cheryl , Thompson Lauren M , Yildiz Mehmet , Henry Timothy D , Quesada Odayme
Published: December 2023

Introduction:
Approximately 75% of women that undergo coronary angiography for angina do not have obstructive disease. However, a significant number have persistent angina, which can reduce their functional capacity and performance, impacting patients’ quality of life. There is a need for further studies that accurately compare angina and functional capacity among women angina with non-obstructive coronary disease (ANOCA).

Objective:
We examined the association between perceived anginal symptoms and functional capacity in patients with ANOCA

Methods:
A the Women’s Heart Center at the Christ Hospital, all women completed the Duke Activity Status Index (DASI) and Seattle Angina Questionnaire-7 (SAQ7) at the initial visit. DASI score range from 0 to 58.2 and assess functional capacity using self-assessment and VO2 peak formula with higher scores indicating better functional capacity. SAQ7 assesses angina symptoms, physical limitation, and quality of life; the score is from 0-100, where a lower score indicates a higher frequency of angina, increased physical limitation, and poor quality of life. DASI and SAQ7 scores were correlated. Sperman correlation and Mcnemar chi-square were used to compare DASI and SAQ7 score results.

Results:
Among 225 women with ANOCA, the mean DASI score was 16.73, and the mean SAQ7 score was 43.79. 63.1% reported a low score of SAQ7, and 79.6% reported a low DASI score. SAQ7 and DASI were moderately correlated (Spearman correlation of +0.42). Further analysis with McNemar chi- square showed that women with lower SAQ7 (score 0-49.4) tends to corresponds with low DASI (score 0-24.5) (Specificity 86.6%), compared to women with higher SAQ7 (score 49.5-100) and high DASI (score 24.6-58.2) (Sensitivity 32.5%) (p<0.001).

Discussion:
Anginal symptoms are correlated with reduced functional capacity among women with ANOCA. Further prospective studies are needed to evaluate the correlation between angina improvement and functional capacity.
Abstract 18280: Five-Year Major Amputation Risk in Patients Undergoing Lower Extremity Bypass Taking into Account All-Cause Mortality Risk and Age Groups
Authors: Romain Gaelle , Cleman Jacob , Mena-Hurtado Carlos , Smolderen Kim G
Published: December 2023

Background:
Selecting good lower extremity bypass (LEB) surgery candidates for chronic limb threatening ischemia (CLTI) is important to optimize risk-benefit ratios for amputation and death. As mortality risks may be different across age groups, we aimed to examine whether amputation risks across age groups differ by their differential competing risk of death.

Methods:
Individuals with CLTI undergoing infrapopliteal LEB from 2014 to 2019 in the Medicare linked Vascular Quality Initiative registry were included. The cumulative incidence Function (CIF) for 5-year mortality and major amputation in age groups <65 and ≥65 years, was calculated by Aalen-Johansen, taking mortality into account, and compared against the CIF derived from a traditional Kaplan-Meier, not accounting for competing death. The major amputation risk by age groups was estimated using a Fine and Gray competing risk model (sHR) accounting for competing death and traditional Cox regression (HR) not accounting for competing death.

Results:
A total of 2,105 patients were included (22% aged <65 years; 70% male, 7% Hispanic, and 18% black). Amputation rates in < 65 vs. ≥65 years were 35.2% and 19.2%; for mortality 34.4% and 44.6%, respectively. In those <65 years, death without amputation was over-estimated by a relative difference of 42%; and major amputation by 16%. Death without amputation in the ≥65 years group was over-estimated by 18%; amputation risk was over-estimated by 23%. When not accounting for competing death risk, adjusted amputation risk for <65 vs ≥65 years was HR 1.17 95%CI 0.90 -1.50 vs. sHR = 1.26 95%CI 0.97-1.62 in the competing risk model. (Table)

Conclusions:
Younger individuals with CLTI have the highest amputation vs. mortality risk; for those older than 65 years it is the other way around. Collapsing estimates across age groups, while not incorporating competing death risk overestimates amputation risk and can mislead the interpretation of therapeutic benefits of CLTI interventions.
Abstract 18281: Identifying Predictors of ICU Mortality Outcomes Among Critically Ill Patients With Atrial Fibrillation Using Machine Learning Models
Authors: Rajan Vijval , Zhang Yanjia , Zhang Zhenwei , Ahmed Md Ashfaq , Roy Mukesh , Ramamoorthy Venkataraghavan , Rubens Muni , Saxena Anshul
Published: December 2023

Introduction:
New onset atrial fibrillation (Afib) is a frequent complication of intensive care admission and is linked to higher mortality in the ICU. We aimed to develop machine learning (ML) models to predict the risk of death in the ICU among these patients and assess their long-term prognosis.

Methods:
Eligible patients with Afib from the Medical Information Mart for Intensive Care IV database were included. The cases were randomly divided into training (75%) and test (25%) groups. Machine learning algorithms such as light GBM, random forest, gradient boosted classifier, and XGBoost were used. In addition, we utilized a tabular deep learning model architecture comprised of an embedding layer for categorical variables. The robustness of the results was ensured through K-fold cross-validation. AUROC and accuracy were used to compare model performance. Models accounted for variables from demographics, labs, charting events, and comorbidity domains. A web-based calculator was also developed to encourage the model's practical application.

Results:
The sample (n = 8455) consisted of 3408 females (40.3%), 6004 whites (71.0%), and 4876 (57.7%) patients with Medicare insurance. The ICU mortality was 9.5% (n = 802). The median age (79 vs. 75 years; p < 0.001) and ICU LOS (4 vs. 2 days; p < 0.001) were higher among the patients who expired. Congestive heart failure was reported in 15% of cases. The lightGBM model (AUROC: 84%) performed best and showed that mean arterial BP, WBC, PO2, platelet count, age, hemoglobin, BUN, pH, ICU LOS and anion gap were the top predictors of ICU mortality among this population.

Conclusion:
Death in the ICU among patients with Afib was associated with several clinical features, especially BP, WBC count, PO2, platelet count, age, and hemoglobin. Predictors of ICU mortality were identified with high accuracy and this may aid in the creation of a real time risk score for selective intervention to reduce the risk of death in this vulnerable patient population.
Abstract 18284: Inhibition of Sulfatase-1 Prevents Pulmonary Arterial Hypertension in Animal Models of Disease
Authors: Samokhin Andriy , Wertheim Bradley M , Alba George A , Arons Elena , Maron Bradley A
Published: December 2023

Introduction:
Sulfatase-1 (Sulf1) is an extracellular enzyme that removes 6-O-sulfate groups from heparan sulfate and is implicated in cardiovascular disease. In human pulmonary artery endothelial cells (HPAECs), Sulf1 mRNA and protein levels are regulated by the fibroproliferative protein NEDD9 involved in PAH.

Hypothesis:
Sulf1 regulates migration and profibrotic potential of HPAECs and its downregulation prevents the development of PAH.

Methods:
HPAECs were transfected with Sulf1 siRNA or adenovirus expressing Sulf1 and cell migration was analyzed by scratch assay. In a PAH disease prevention treatment protocol, rats received intratracheal injection of Sulf1 siRNA (si-Sulf1) (1mg/kg of body weight, once a week for 3 weeks) beginning one day following the administration of monocrotaline (MCT). In a disease reversal protocol, injection of si-Sulf1 (1mg/kg of body weight, once every 5 days for a total of 3 doses) began 14 days following initiation of SU-5416/Hypoxia (SU/Hypox) PAH model.

Results:
Overexpression of Sulf1 in HPAECs resulted in a significant reduction in migration compared to empty vector (wound size 506 ± 39 vs 353 ± 19 μm, P<0.01), whereas transfection with si-Sulf1 increased migration significantly compared to si-Scrambled control (wound size 212 ± 30 vs 295 ± 31 μm, P<0.01). Overexpression of Sulf1 also increased extracellular collagen III deposition in cultured HPAECs compared to empty vector (15.4 ± 5 vs. 7 ± 1 arb. units, P<0.01). Immunostaining of HPAECs for Sulf1 showed strong expression at focal adhesions. In both
in vivo
PAH models, si-Sulf1 treatment significantly decreased right ventricular (RV) systolic pressure compared to si-Scrambled control (MCT: 41 ± 5 vs 58 ± 6 mm Hg, P<0.05; SU/Hypox: 40 ± 5 vs 75 ± 15 mm Hg, P<0.05) and RV mass measured by Fulton index (MCT: 0.33 ± 0.06 vs 0.56 ± 0.06, P<0.01; SU/Hypox: 0.32 ± 0.02 vs 0.41 ± 0.02, P<0.05).

Conclusions:
These data demonstrate that pulmonary endothelial expression of Sulf1 is increased at focal adhesions and regulates cellular migration. Inhibition of Sulf1 significantly reduced the severity of PAH
in vivo,
which, taken together, identifies Sulf1 as a potential therapeutic target by which to improve proliferative vascular remodeling and pulmonary hypertension in PAH.
Abstract 18290: Enhancing Outcomes in Dyslipidemia Management: Contemporary Insights and Perspectives From the Indian Consensus
Authors: Shah Jay , Meena Chandra B , Kannan BRJ , Ahmad Sajan , Barkotoky Ritankur , Kumar R Pradeep , Ghosh Gopal C , Chakraborty Saujatya , Tyagi Kavita , Sharma Rajat , Prasad K Aravinda , Pandya Rashmit , Sharma Amit V ,   STRATIFY 2 Consensus Group
Published: December 2023

Introduction:
To establish a comprehensive consensus statement on dyslipidemia management, incorporating contemporary evidence and drawing from the valuable real-world experiences of Indian physicians and cardiologists

Methods:
A virtual collaborative educational initiative was convened in May 2023, through a series of 13 nationwide virtual interactive meetings (n=238) at the forefront of dyslipidemia management (STRATIFY 2 Consensus Group). The cumulative clinical experience was approximately 6,000 man years, who rated their level of agreement for 10 questions with each item on a 5-point Likert scale. This was preceded by a contemporary evidence-based discussion on the updates for dyslipidemia including statins. Weighted mean for the Likert scale was calculated and consensus was pre-defined as a score > 100. GraphPad 9.5.1 and ANOVA were used for statistical analysis.

Results:
The highest agreement score was for, using LDL-C as a performance measure enhances cholesterol control in high-risk groups, leading to reduced cardiovascular disease morbidity and mortality (119), attainment of LDL-C goals in patients receiving high-intensity statin therapy needs improvement in real-world settings (116), combination of short-term DAPT and intensive rosuvastatin reduces the risk of recurrent stroke (113), validated risk calculators such as QRISK3 are valuable tools for guiding clinical decisions regarding the initiation of statin therapy (112), rosuvastatin 40 mg daily is more effective in reducing LDL-C levels as compared to atorvastatin 80 mg (110), Rosuvastatin is more effective than Atorvastatin in reducing LDL-C levels in diabetes mellitus (104) (Figure). The highest mean response scores (±SD, 95% CI) for consensus were for agree (61±25, 95% CI 44 to 80) followed by strongly agree (32±17, 95% CI 20 to 44)

Conclusions:
The consensus findings contribute to advancing dyslipidemia management and guiding evidence-based practices for improved patient outcomes.
Abstract 18307: Causal Association Between Gut Microbiota Composition and the Risk of Atrial Fibrillation
Authors: Wang Jingyang , Tan Jiangshan , Yang Yanmin
Published: December 2023

Background:
Considerable evidence has shown that alterations in gut microbiota composition are associated with atrial fibrillation (AF). However, the causal associations remain largely unresolved. This study aims to reveal the causality between gut microbiota and AF.

Method:
We incorporated data from the largest genome-wide association studies (GWASs) of gut microbiota composition including a sample of 18,304 individuals and AF compared a total of 60,620 cases and 970,216 controls of European ancestry. A two-sample Mendelian randomization framework was designed to investigate the involvement of gut microbiota in AF.

Results:
Among all gut microbiota, four microbial taxa, namely Lachnospiraceae FCS020 group (OR: 1.077; 95% CI: 1.011- 1.148; P= 0.021), Rikenellaceae_ RC9_ gut_ group (OR: 1.047; 95% CI: 1.010- 1.086; P= 0.012), Catenibacterium (OR: 1.060; 95% CI: 1.002-1.122; P= 0.043), Victivallis (OR: 1.038; 95% CI: 1.001- 1.077; P= 0.044), and Erysipelatoclostridium (OR: 1.344; 95% CI:1.095-1.649; P= 0.014), were identified to be causally associated with the higher risk of AF. Besides, genetically predicted five microbial taxa, namely Lachnospiraceae NK4A136 group (OR: 0.918; 95% CI: 0.865- 0.973; P= 0.004), Howardella (OR: 0.948; 95% CI: 0.910- 0.989; P= 0.012), Intestinibacter bartlettii (OR: 0.933; 95% CI: 0.879- 0.991; P= 0.024), Alloprevotella (OR: 0.942; 95% CI: 0.896-0.992; P= 0.022), Anaerostipes (OR: 0.922; 95% CI: 0.857-0.992; P= 0.030), Odoribacter (OR: 0.910; 95% CI: 0.831- 0.996; P= 0.041), Ruminococcus (gnavus group) (OR: 0.952; 95% CI: 0.908- 0.999; P= 0.044), and Ruminiclostridium 5 (OR: 0.678; 95% CI: 0.486- 0.947; P= 0.046), can prevent AF.

Conclusions:
Our study provides evidence of the causal effect of the gut microbiota on AF, highlighting causal microbial taxa. Our results may offer novel insights into gut microbiota-mediated mechanisms and interventions of AF.
Abstract 18327: Influence of Microtubule Detyrosination on Left Atrial Myopathy in a Rat Model of Heart Failure With Preserved Ejection Fraction
Authors: Smolyak Julia N , Eaton Deborah M , Hached Khaled , VAN DER LAAN Siem , Prosser Benjamin L , Margulies Kenneth B , Lee Benjamin W
Published: December 2023

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is characterized in part by increased left ventricular (LV) stiffness and left atrial (LA) remodeling. LA myopathy in HFpEF is associated with poor clinical outcomes. In the LV, the magnitude of post-translational detyrosination of α-tubulin, regulated by vasohibins (VASH1/2), contributes to LV stiffness. However, the role of tubulin detyrosination in the LA is currently unknown. To this end, we assessed the extent of LA myopathy in the ZSF rat model of HFpEF, and assessed the effect of acute VASH inhibition on LA remodeling.

Methods:
ZSF obese rats with diastolic dysfunction were compared alongside ZSF lean hypertensive-only rats and Wistar Kyoto rats (WKY). Rats were aged to 30 weeks, then received a tail vein injection of VASH inhibitor or vehicle, followed by echocardiography. Following a second injection, hearts were excised, and LA and LV were separated for downstream protein analysis.

Results
: ZSF obese rats develop hallmark features of HFpEF including preserved systolic function, left ventricular hypertrophy, and slowed relaxation compared to lean and WKY. ZSF obese animals demonstrated significant LA myopathy, including increased LA area, reduced LA emptying fraction, and reduced LA strain. Acute VASH inhibition led to trends towards normalization of LA kinetics. There were no significant differences in levels of detyrosinated tubulin between vehicle and VASH inhibition groups in the LA, though there was a significant reduction of detyrosinated tubulin in the LV by Western Blot (detyrosinated tubulin / GAPDH relative quantity Vehicle: 1.5±0.2 vs. VASH inhibitor 0.5±0.1; p<0.05).

Conclusions:
Acute VASH inhibition improves LA kinetics in ZSF obese rats secondary to reductions in detyrosinated tubulin in the LV. Future studies employing sustained reductions of detyrosinated tubulin may lead to better understanding of LA-LV interactions in the pathogenesis of LA myopathy in HFpEF.
Abstract 18338: TBX4 Loss-of-Function Within the Embryonic Lung Mesenchyme Disrupts Postnatal Lung Development and Increases Susceptibility to Pulmonary Hypertension
Authors: Maldonado Velez Gabriel , Cook Todd , Aldred Micheala A
Published: December 2023

Introduction:
The T-box 4 (TBX4) transcription factor is recognized as a risk gene in pulmonary arterial hypertension (PAH). TBX4 is expressed within the lung mesenchyme in the developing lung and is required for lung branching morphogenesis. Genetic studies report that PAH cases with
TBX4
mutations display an earlier onset of the disease. In addition, studies have reported carriers of
TBX4
mutations with diffused alveolar development and pulmonary hypertension (PH). Currently, there is a lack of evidence on the effect of TBX4 loss-of-function (LoF) on later stages of lung development and predisposition to lung disease.

Hypothesis:
Lung mesenchyme
Tbx4
deletion within the developing lung disrupts essential gene regulatory networks leading to abnormal postnatal lung development and susceptibility to pulmonary hypertension.

Methods:
We have generated
Tbx4
conditional knockout (
Tbx4-CKO
) mice in which
Cre
recombinase
removes the exon 5 of
Tbx4
within the embryonic lung mesenchyme, creating a null allele. To examine alveolarization, we harvested postnatal day 14 (P14) and 36 (P36) lungs and calculated mean linear intercept (MLI). RNA-seq was performed at both stages to identify disrupted gene networks in
Tbx4-CKO
lungs. RVSP was measured by right heart catheterization in six-month-old mice to evaluate for PH.

Results:
Tbx4-CKO
lungs show increasing alveolar simplification at P14 and P36, as confirmed by increases in MLI of 24.8% and 34.4%, respectively.
Tbx4-CKO
mice show a statistically significant increase of 10.4% in RVSP, and preliminary analysis of vessel wall thickness suggests mild vascular remodeling in their lungs. RNA-seq analysis shows enrichment of pathways (canonical WNT, VEGF, and BMP signaling) and genes (
Lgr5
,
Tnc
,
Wnt3a
,
Areg
,
Gdf2
, and
Bmper
) relevant to lung alveologenesis, angiogenesis, and PH.

Conclusions:
TBX4 LoF affects lung alveolar development, similar to observations made in human cases with
TBX4
mutations. The clinical presentation of such cases is broad, but our mice show features of bronchopulmonary dysplasia, including alveolar simplification and PH. Further analysis of our RNA-seq data and planned single-cell analyses should provide insight into the role of TBX4 in alveolarization and PH risk.
Abstract 18348: Causes and Predictors of 30-Day Readmissions Following Permanent Pacemaker Implantation in Patients With Cardiac Amyloidosis: From National Readmission Database (2016-2020)
Authors: Gajjar Rohan , Bittar Carlini Gianfranco , Vardar Ufuk , Karki Sadichhya , Teaima Taha , Patel Bhavin A , Kumar Manoj , Vij Aviral
Published: December 2023

Introduction:
Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy where local deposition of amyloid fibrils causes heart failure, arrhythmias, and conduction system abnormalities. Involvement of the AV nodal and infra-hisian conduction system increases the need for a permanent pacemaker (PPM). Studies have noted worse outcomes in patients with implantable-cardioverter defibrillator placement in amyloidosis, but a comparison with PPM is lacking. We sought to analyze readmissions in CA patients following PPM placement utilizing National Readmission Database (NRD).

Methods:
NRD (2016 to 2020) was queried to identify adults with a diagnosis of CA who underwent PPM implantation using ICD-10 CM and PCS codes. The primary outcome was a 30-day readmission rate. Secondary outcomes were in-hospital mortality, length of stay (LOS), total hospital charge (THC), and predictors of readmission. Multivariate/univariate logistic and linear regression analyses were used to analyze the outcomes and adjust for possible confounders.

Results:
A total of 1,027 encounters of CA who underwent PPM were identified, of which 975 were discharged alive. Within 30 days from discharge, 141 (14.5%) were readmitted. Those readmitted had a longer LOS and higher burden of comorbidities while were similar in age, sex, hospital characteristics, and household income status. Readmissions lead to an additional mean THC of $55,079 and a mean LOS of 6.3 days. The top five causes of readmissions were heart failure (23%), sepsis (6.6%), hypertensive heart disease (4%), bradycardia (3.5%), and acute kidney injury (3.2%). Figure-1 shows the forest plot of a multivariate analysis of independent factors associated with readmissions.

Conclusions:
Our findings show that up to 15% of patients with CA who undergo PPM implantation get readmitted with heart failure being the most common etiology. Optimizing comorbidities with PPM implantation in CA may provide better outcomes and reduce admissions.
Abstract 18349: The Impact of Concomitant Mitral Regurgitation on Aortic Valve Intervention Outcomes in Paradoxical Low-Flow Low-Gradient Severe Aortic Stenosis
Authors: Dahan Shani , Dal-Bianco Jacob , Plakht Ygal , Namasivayam Mayooran , Zeng Xin , Passeri Jonathan , Yucel Evin , Picard Michael H , Levine Robert , Hung Judy
Published: December 2023

Background:
Patients with paradoxical low flow low gradient severe aortic stenosis (LFLGAS) exhibit low transvalvular flow rates due to reduced stroke volumes, while maintaining preserved left ventricular ejection fraction (LVEF). The presence of mitral regurgitation (MR) adds complexity to this already challenging diagnosis, by further lowering flow rate. However, the impact of aortic valve intervention in this patient population remains uncertain.

Methods:
A total of 1178 patients were included from an institutional echo database with adjudicated aortic valve area (AVA <1.0 cm2), transaortic gradients (mean gradient< 40 mmHg) and low flow rate (Q ≤210 ml/sec), to confirm the diagnosis of LFLGAS and preserved LVEF (>50%). Subgroups were formed based on the presence of severe MR and subsequent surgical and transcatheter aortic valve intervention (SAVR/TAVR). Patients who underwent mitral valve intervention were censored. All-cause mortality was assessed as the primary outcome.

Results:
Patients with severe MR had significantly lower flow rates compared to patients w/o severe MR (166.5 ± 26.3 vs 174.7 ± 25, p=0.006). During a median follow up of 1.3 years, 745 deaths (62.2%) were identified, with a cumulative incidence significantly lower in the intervention groups (Figure). After multivariate propensity adjustment for age, sex, aortic valve area and comorbidities, aortic valve intervention showed a significant reduction in mortality risk in both intervention groups, which was more pronounced in the severe MR group compared to patients w/o severe MR (AdjHR 0.334, p=0.015 vs 0.436, p<0.001, p for interaction =0.24).

Conclusions:
In paradoxical low-flow low-gradient severe aortic stenosis, aortic valve intervention results in a survival benefit, especially among patients with concomitant severe MR. Our findings highlight the importance of recognizing severe MR as a flow-diverting lesion that can impact outcomes in LFLGAS.
Abstract 18350: COVID-19 Patients With Pulmonary Hypertension Hospitalized in the United States During the Early Pandemic: Analysis of In-Hospital Mortality, Clinical Outcomes, and Racial Disparities
Authors: Majeed Harris
Published: December 2023

Introduction:
Coronavirus Disease 2019 (COVID-19) has been associated with adverseoutcomes among hospitalized patients with pulmonary hypertension (PH) based onlimited studies. The objective of our retrospective study was to utilize theNational Inpatient Sample (NIS) database to compare in-hospital mortality andother secondary clinical outcomes between COVID-19 patients with PH andCOVID-19 patients without PH.

Hypothesis:
We hypothesizedthat there would be a significant increase in inpatient mortality and othercomplications among hospitalized COVID-19 patients with PH.

Methods:
Patientsages 18 years and older admitted to a hospital in the United States betweenJanuary 1, 2020 and December 31, 2020 with COVID-19 were included in our studyand stratified into two cohorts.

Results:
Aftermultivariate adjustment, we found that COVID-19 patients with PH hadsignificantly higher in-hospital mortality, increased lengths of stay, andhigher costs of hospitalization when compared to COVID-19 patients without PH.We also noted that COVID-19 with PH had increased dependence on invasive andnon-invasive positive pressure ventilation suggestive of more severerespiratory failure. Furthermore, our data demonstrated that COVID-19 patientswith PH were at risk of pulmonary embolism and myocardial infarction. Also,Hispanic and Native American COVID-19 patients with PH remained at anindependently elevated risk for in-hospital mortality when compared to otherracial groups.

Conclusions:
To our knowledge this isthe largest study evaluating outcomes among COVID-19 patients with PH.In-hospital complications, especially pulmonary embolism, present a clinicalmechanism for the observed inpatient mortality. Given the significant mortalityand complications associated with COVID-19 infection and pulmonaryhypertension, we recommend vaccination against SARS-CoV-2 and aggressivenon-pharmacologic preventative measures.
Abstract 18372: Peripheral Intravascular Lithotripsy to Facilitate Transfemoral Transcatheter Aortic Valve Replacement - Updated Outcomes
Authors: Tom Stephanie , Tully Andy , Devireddy Chandan , Grubb Kendra
Published: December 2023

Background:
Transfemoral transcatheter aortic valve replacement (TF-TAVR) approach has proven to be superior to alternative access[1]. However, a subset of patients being evaluated for TF-TAVR are deemed unfit secondary to peripheral arterial disease. Despite reduction of delivery system profiles to 14 - 18 Fr, current systems still pose an increased risk of access vessel injury. For patients anatomically unfit for standard transfemoral access, peripheral intravascular lithotripsy (IVL) has emerged to facilitate femoral access for TAVR.

Methods:
Single center, retrospective analysis of an institutional patient database, queried from 1/2018 through 12/2022 for all patients undergoing TAVR. All patients undergoing IVL facilitated lithotripsy for transfemoral access were analyzed.

Results:
A total 2,209 TAVR cases were identified, with 75 (3.78%) having undergone lithotripsy: 14 in 2018, 15 in 2019, 16 in 2020, 13 in 2021, and 17 in 2022. The lithotripsy cohort consisted of 45% female with mean age of 78±9.8 years. Average length of stay was 3 days. Common and external iliac lesions were the most common target (n=41/75), followed by common iliac alone (n=25/75). Majority of IVL was performed with 7-mm lithotripsy catheter (n=55/75). Procedural success was 98.7% (n=74/75). Average fluoroscopy time 31 minutes, and average total contrast infusion 87cc. Average number of pulses per lesion was 260 ±52. Mean target lesion diameter on the right 5.0 ±1.2mm and left 5.3 ±1.3mm. Average aortic valve calcium score was 2405.6 ±1260.4. Total complication rate was 28%. Complications requiring secondary vascular procedure occurred in 5.3% (n=4/75) with femoral stenosis requiring balloon dilation, external iliac pseudoaneurysm and retroperitoneal bleed secondary to common femoral pseudoaneurysm primarily repaired, and CFA occlusion required open endarterectomy. Mortality at 30-days 1.3% (n=1/75).

Conclusions:
This abstract aims to provide an updated report of a single institution experience for the use of IVL to facilitate transfemoral TAVR. The IVL facilitated TF-TAVR is feasible, safe, and effective at preserving the transfemoral TAVR route in patients with severe peripheral artery disease.

[1] Holmes. et al.
J Am Coll Cardiol,
2015. 66(25): p. 2813-2823
Abstract 18373: Differential Effects of Hypertension and Aneurysm on Stiffness Properties of the Abdominal Aorta
Authors: Figueroa Mario , Gedney John , Mattia Victoria , xiong Ying , Mukherjee Rupak , Jones Jeffrey A , Ruddy Jean Marie
Published: December 2023

Introduction:
The serum and glucocorticoid inducible kinase-1 (SGK-1) can contribute to matrix remodeling in murine models of hypertension (HTN) and abdominal aortic aneurysm (AAA), a potential biomechanical link between these aortopathies. Utilizing aortic stiffness as a marker of pathologic remodeling.
Hypothesis:
We hypothesize that HTN causes an SGK-1 dependent increase in aortic stiffness to amplify AAA growth.
Methods:
AngiotensinII (AngII) infusion induced HTN in C57Bl/6 mice (WT;1.46mg/kg/day) with subset groups treated + periadventitial CaCl2 to induce AAA and + infusion of the specific SGK-1 inhibitor EMD638683 (2.5mg/kg/day;n=2-4 each). Abdominal aortic ultrasound was conducted on Day 0 and Day 21 to measure stiffness parameters (radial strain(RS), distensibility(D), pulse propagation velocity(PPV)). Aortic diameter (AoD) was obtained by ultrasound and systolic blood pressures (SBP) were measured by Coda tail cuff.
Results:
This HTN model has consistently resulted in >30% increase in SBP and AAA induction did not effect SBP. Although the WT+AngII+AAA mice had 66+8% increase in AoD, dilation was not amplified beyond that of the WT+AAA mice (72+7%, p=NS). Treatment with EMD had no impact on SBP, but did significantly reduce AAA growth (WT+AAA+EMD=29+5%; WT+AngII+AAA+EMD= 24+3%), therefore despite ongoing mechanical tension, SGK-1 inhibition abrogated a pathway necessary for degenerative remodeling. Accordingly, aortic stiffness was differentially altered in HTN versus AAA. As indictors of increased stiffness, D decreased with HTN (p<0.05 vs Day 0) and RS decreased with AAA (p<0.05 vs Day 0), but SGK-1 inhibition had no effect, indicating that the matrix remodeling driving these mechanical parameters was not SGK-1 dependent. Conversely, PPV was increased in both aortopathies (WT+AAA, WT+AngII, WT+AngII+AAA; each p<0.05 vs Day 0) but EMD infusion prevented elevation in PPV, suggesting SGK-1-dependent preservation of contractility.
Conclusions:
Although concurrent induction of HTN and AAA did not amplify AAA growth, these aortopathies differentially impacted aortic stiffness. Tracking PPV as an indicator of pathologic SGK-1 activity may represent a pharmacological target to abrogate dysfunctional aortic remodeling.
Abstract 18382: Clinical and Genetic Associations of Deep-Learning Estimated Peak Oxygen Consumption From the Resting 12-Lead Electrocardiogram
Authors: Khurshid Shaan , Churchill Timothy , Weng Lu-Chen C , Pirruccello James , Friedman Samuel , Diamant Nathaniel , Reeder Christopher , Singh Pulkit , Maddah Mahnaz , Philippakis Anthony A , Baggish Aaron , Ho Jennifer E , Guseh James S , Ellinor Patrick T
Published: December 2023

Introduction:
Oxygen consumption at peak exercise (VO2
peak
) is the gold standard for cardiorespiratory fitness, but prior genome-wide association studies (GWAS) have been limited by the availability of cardiopulmonary exercise testing (CPET). Recent deep learning methods to estimate VO2
peak
from the resting 12-lead electrocardiogram (ECG) may enhance genetic studies of cardiorespiratory fitness.

Methods:
We applied a validated deep learning model (Deep ECG-VO2) to estimate VO2
peak
among UK Biobank participants with a 12-lead ECG. We assessed for associations between estimated VO2
peak
and incident hypertension, diabetes, and atrial fibrillation (AF) using Cox proportional hazards models adjusted for age and sex, and plotted cumulative risk of each outcome stratified by tertile of estimated VO2
peak
. We then performed a multi-ancestry GWAS of estimated VO2
peak
using BOLT-LMM, adjusted for age, sex, array, and the first five principal components of ancestry. Candidate genes were prioritized based on proximity to the lead variant.

Results:
We applied Deep ECG-VO2 to estimate VO2
peak
using the resting 12-lead ECG of 40,801 UK Biobank participants (age 65±8, 52% women). Greater estimated VO2
peak
was associated with lower risks of hypertension (hazard ratio per 1-standard deviation 0.76, 95% CI 0.70-0.83), diabetes (0.60, 95% CI 0.53-0.67) and AF (0.82, 95% CI 0.74-0.90). Cumulative risk of each outcome was higher with decreasing estimated VO2
peak
(
Figure
). In a GWAS of estimated VO2
peak
within 39,716 participants with genetic data (age 65±8, 52% women, 90% European), we identified 10 novel genome-wide significant loci, including variants near genes involved in cardiac structure (
CCDC141/TTN, BAG3)
, cardiac conduction (
SCN5A
), and adiposity (
FTO
).

Conclusions:
Leveraging artificial intelligence-enabled estimation of VO2
peak
from the resting 12-lead ECG, we identify 10 novel common genetic variants associated with cardiorespiratory fitness.
Abstract 18383: Body Composition Changes in Peak Oxygen Uptake Responders and Non-Responders During Cardiac Rehabilitation
Authors: Sharif Salaheddin M , Taylor Jenna L , Bonikowske Amanda , Olson Thomas P
Published: December 2023

Introduction:
Cardiac rehabilitation (CR) is known to improve peak oxygen uptake (VO
2
peak) and body composition (BC). However, not all CR patients improve VO
2
peak and it remains unclear if non-responders also exhibit limited improvement in BC. This study aimed to examine if non-responders to VO
2
peak also demonstrate limited improvement in BC and whether BC is related to VO
2
peak changes in CR patients.

Methods:
Retrospective analysis of patients who completed CR between 2015 and 2022 at Mayo Clinic. The study included 143 patients who completed both dual-energy X-ray absorptiometry and cardiopulmonary exercise testing before and after CR. Patients were grouped by VO
2
peak response to CR (36 non-responders=Δ≤0 vs 107 responders=Δ>0 mL/kg/min). Within and between-group differences were assessed by paired and independent t-tests respectively. Regression models were used to evaluate whether baseline BC or ΔBC predict VO
2
peak changes.

Results:
As an entire cohort there were significant mean improvements in VO
2
peak and BC (Table 1, p<0.05). VO
2
peak increased in 75% of patients (responders: Δ 2.9±2 vs non-responders: Δ -2.1 ±2, mL/kg/min, p<0.05). There were no significant differences in baseline characteristics between groups including BC (Table 2, p>0.05); however, non-responders had significantly shorter duration and exercise sessions compared to responders (Table 2, p<0.001). Non-responders for VO
2
peak exhibited a significant improvement in body fat mass, body lean percentage, body fat percentage, and fat mass index (all p<0.001), with no differences in ΔBC between groups (Table 3). Regression models revealed no significant BC predictors for VO
2
peak.

Conclusion:
Despite significant improvements in BC, 25% of patients did not improve VO
2
peak with CR. These data suggest VO
2
peak improvement is not related to baseline BC or change in BC. These findings suggest the need for additional strategies to maximize improvements in VO
2
peak for patients undergoing CR.
Abstract 18392: Sedentary Behavior and Risk of 1-Year Cardiac Events and Mortality After Suspected Acute Coronary Syndrome
Authors: Diaz Keith M , Boudreaux Benjamin , Xu Chang , Sanchez Gabriel , Murdock Margaret , Cruz Gaspar , Jurado Ammie , Gonzalez Alvis , Ellis Julia , Diaz Franchesca , Chang Melinda , Romero Emily , Scott Allie , Sullivan Alexandra , Duran Andrea , Kronish Ian M , Edmondson Donald
Published: December 2023

Background:
Patients hospitalized with acute coronary syndrome (ACS) remain at high risk for recurrent cardiac events in the first year after discharge, necessitating a need to identify modifiable targets to improve outcomes. While moderate-vigorous physical activity (MVPA) is a hallmark of secondary prevention in this population, sedentary behavior (SB) has emerged as a potentially unique aspect of the physical activity profile that may also have prognostic relevance. Yet little is known regarding whether SB confers risk independent from MVPA and what types of activity should be substituted for SB to impart health benefit among ACS patients in the first year after discharge.
Aim:
Examine the association between SB and risk of 1-year cardiac events and mortality among patients evaluated for ACS.

Methods:
Patients (n=609, 52% male, 62 ± 13 y) evaluated in the emergency room for ACS were fitted with a GENEActiv wrist accelerometer in-hospital and wore the device for 30 days post discharge to measure SB, light intensity physical activity (LIPA), MVPA, and sleep. Major adverse cardiovascular events 1-year post discharge were defined as the composite of unstable angina, myocardial infarction, or death.

Results:
Over follow up, 50 patients (8%) had a major adverse cardiovascular event. SB was associated with an increased risk of 1-year major adverse cardiovascular events after adjusting for demographic and disease severity indicators (HR per 1 h/d increase: 1.33, 95% CI: 1.12, 1.58). The association remained significant after adjusting for MVPA (HR per 1 h/d increase: 1.30, 95% CI: 1.06, 1.59). In isotemporal substitution analyses there were beneficial associations for replacing SB with sleep (per 30 min HR: 0.89, 95% CI: 0.81, 0.97), LIPA (per 30 min HR: 0.51, 95% CI: 0.34, 0.76), and MVPA (per 30 min HR: 0.32, 95% CI: 0.12, 0.85) on 1-year major adverse cardiovascular event risk.

Conclusion:
SB was associated with increased risk of 1-year cardiac events and mortality among patients evaluated for ACS, independent of MVPA. Replacing SB with sleep, LIPA, or MVPA was associated with lower risk. These findings suggest reducing SB may improve outcomes in ACS survivors and support the public health message that ACS patients should sit less and move or sleep more to mitigate risk.