bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14493: Association of Circulating Ketone Bodies With Cognitive Performance and Dementia in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Chevli Parag A , Schaich Christopher L , Shemesh Elad , Wood Alexis , Connelly Margery , Thazhathuveetil Kunahamed Luqman Arafath , Mehta Anurag , Jain Vardhmaan , Craft Suzanne , Hughes Timothy M , Shapiro Michael D
Published: December 2023

Introduction:
There is growing interest in the association between circulating ketone bodies (KB) and cognitive function, especially in the context of aging and neurodegenerative diseases.
Aim:
To examine the prospective association of KB with cognitive performance and clinical dementia among participants without baseline cardiovascular disease (CVD).

Methods:
KB were measured in 6786 MESA participants by nuclear magnetic resonance spectroscopy at Exam 1 (2000-02). Plasma levels of the 3 ketone bodies (β-hydroxybutyrate, acetoacetate, and acetone) were summed as total KB. Cognitive performance was assessed in 4392 participants at Exam 5 (2010-12) by the Cognitive Abilities Screening Instrument (CASI), Digit Symbol Coding (DSC), and Digit Span (DS) tests and re-administered to a subset (n=1838) at Exam 6 (2016-18). We examined the association of total KB with Exam 5 cognitive test performance and with the change in scores from Exam 5 to Exam 6 using multivariable linear regression. Multivariable-adjusted Cox proportional hazard models were used to examine the association of total KB with incident dementia. Incident dementia was identified by ICD codes at hospitalization or death (2000-2018)

Results:
A total of 6786 participants were included in the analysis (mean age 62 (10) years at Exam 1, 53% women, 61% non-White). There were 585 incident dementia events over a median follow-up of 16.7 yrs. In a fully adjusted model, a doubling of total KB was associated with a greater risk of incident dementia [HR (95% CI): 1.21 (1.05-1.39)]. Total KB were associated with worse Exam 5 DS performance [β (95% CI): -0.28 (-0.44,-0.12)]. However, we did not find an association between total KB and a decline in cognitive performance (
Figure
).

Conclusion:
In a multi-ethnic population free of baseline CVD, elevated KB levels were associated with incident dementia and worse performance on a test of working memory.
Abstract 14498: Predictive Value and Optimal Cut-Off High-Sensitivity Troponin T Levels in Patients With Acute Pulmonary Embolism
Authors: Kim Moojun , Seo Chang-Ok , Kim Hangyul , Kim Hye Ree , Kim Kyehwan , Koh Jin-sin , Hwang Seok-Jae , Hwang Jinyong , Park Jeong Rang
Published: December 2023

Introduction:
An elevated troponin level serves as a sign of myocardial injury in cases of acute pulmonary embolism (PE) and is considered one of the factors used to assess risk and determine thrombolytic therapy. Nonetheless, high-sensitivity troponin (hsTnT) has not been extensively researched among patients with acute PE.

Hypothesis:
The elevation of hsTnT levels could predict adverse outcomes in acute PE.

Methods:
A retrospective chart review of 307 patients who were diagnosed with acute PE from July 2020 to April 2023 was conducted. All patients were confirmed by computed tomography pulmonary angiography. The 30-day adverse outcome was defined as a composite of PE-related mortality, cardiac arrest, hemodynamic collapse, and vasopressor use. Youden-index quantification was used to identify the optimal hsTnT cut-off value. The echocardiographic right ventricular dysfunction signs and electrocardiographic findings were collected at baseline examinations.

Results:
HsTnT values ranged from 3 to 1152 ng/L [median 33 (25
th
-75
th
percentile 15-78) ng/L]. Receiver operating characteristic curve analysis for the 30-day adverse outcome showed moderate significance (AUC 0.68 (95% CI 0.60-0.81) (Fig. 1). The optimal hsTnT cut-off value was 33 ng/L. Patients with hsTnT ≥ 33 ng/L were characterized by advanced age, lower blood pressure, higher creatinine, and exhibited signs of right ventricular dysfunction. The hazard ratio of hsTnT ≥ 33 ng/L for adverse outcomes was 3.69 (95% CI 1.62-8.40) (Table 1).

Conclusion:
We refined the predictive value of troponin in acute PE, and suggest the level hsTnT ≥ 33 ng/L as an optimal cut-off value for the prediction of the 30-day adverse outcomes.
Abstract 14501: Process Evaluation of a Double Blind Randomized Controlled Trial to Assess the Efficacy and Safety of a Quadruple Ultra-Low-Dose Treatment for Hypertension Within a Federally Qualified Health Center Network (QUARTET USA)
Authors: Sanuade Olutobi A , Jacobson Tyler A , Quintana Adriana , Flowers Fallon , Lazar Danielle , Vu My , Mejia Jairo , Ciolino Jody , Huffman Mark D , Kandula Namratha
Published: December 2023

Introduction:
This explanatory sequential mixed-methods process evaluation of the QUARTET USA clinical trial (NCT03640312) explores patient and health professional perceptions about the use of low-dose quadruple therapy (LDQT) as a novel strategy for hypertension management.

Methods:
Sixty-two patients took part in the trial. Survey data were collected from patients to understand their beliefs about blood pressure medications and treatment satisfaction with LDQT. A sub-sample of 13 English and Spanish patients and 11 health professionals, recruited via purposive sampling, took part in semi-structured qualitative interviews. Data collection took place between August 2019 and July 2022. Quantitative data were analyzed using descriptive statistics and cross-tabulations, and the qualitative data were analyzed using thematic analysis. Common themes from the two sets of findings were integrated.

Results:
54.3% of patients believed in the necessity of their blood pressure medicines and 40.6% were concerned about the side effects and long-term effects of their medications. At trial completion, 80.4% of the patients were satisfied with the LDQT, 96.4% were certain the benefits of taking LDQT outweighed the disadvantages, and all participants reported that it was convenient to take. Both patients and health professionals found LDQT acceptable because it facilitated patients’ blood pressure control and medication adherence, and reduced patients’ perceived pill burden and adverse reactions. Health professionals stated that a limitation of LDQT was the inability to titrate the dose and that health insurance coverage and inclusion of LDQT in national hypertension guidelines could increase its widespread use.

Conclusions:
The LDQT strategy was acceptable to patients and health professionals for hypertension treatment. While LDQT therapy generally improved and maintained patients’ blood pressure control, medication adherence, and had a good safety profile, the limitation of its titration inflexibility and medication cost were raised by health professionals. Making LDQT therapy flexible by introducing stepped care combinations and ensuring health insurance coverage could increase its widespread implementation and scale-up.
Abstract 14514: Hypertrophic Cardiomyopathy - Genotype Distribution and Genotype-Phenotype Correlations - A Unique Perspective From a Single Center Study
Authors: Ashraf Muddasir , Jan M F , Jahangir Arshad , Kroboth Stacie , Walczak Sara , Sanders Heather , Tajik A. Jamil
Published: December 2023

Background:
The role of genotype in risk stratification of hypertrophic cardiomyopathy (HCM) is unclear.

Hypothesis:
Genotype status affects phenotype and associated outcomes.

Aims:
To evaluate genotype-phenotype correlations in all adult HCM patients seen at our Cardiac Specialty Center over 13 years and associated outcomes.

Methods:
We evaluated genotype-phenotype correlations, all-cause mortality, and a composite outcome, including mortality, stroke, implantable cardioverter-defibrillator placement, heart failure hospitalization, LV assist device implantation, heart transplant, septal myectomy, and alcohol septal ablation.

Results:
Of 827 HCM patients, genotyping was completed in 754 (91.2%), which included 27% genotype-positive (Gen-P), 22% variants of unknown significance (VUS), and 51% genotype-negative (Gen-N) patients with a mean age of 47, 57, and 58 years, respectively. The most common gene implicated was
MYBPC3
(63%). LV hypertrophy on electrocardiogram was more frequent in Gen-N than Gen-P patients. Gen-P patients had more frequent non-sustained ventricular tachycardia on Holter monitoring (25% vs 10%), grade III diastolic dysfunction (12% vs 7%), elevated ProBNP (71% vs 61%), and lower ejection fraction (66% vs 69%) than Gen-N patients (P <.05 for all comparisons). All heart transplantations (N=5) were performed in Gen-P patients. LVOT obstruction was more frequent in Gen-N than Gen-P patients (48% vs 26%, P <.01). Distribution of outcomes is shown in Panels A-H. The composite outcome was worse in Gen-P vs Gen-N patients (HR 1.84, P <.01). The other independent predictors of poor composite outcome were old age, male sex, obesity, and atrial fibrillation. A separate analysis of mortality showed similar survival in all groups.

Conclusion:
Differences exist in phenotype and outcomes based on the genotype status, with more severe phenotype and poorer outcomes in Gen-P patients in our single-state single-center experience.
Abstract 14516: Combined Platelet Morphology and Clinicoradiological Features to Predict Type II Endoleaks Following Endovascular Abdominal Aortic Aneurysm Surgery
Authors: Pratama Muhammad Yogi , King Benjamin , Teter Katherine , Bi Christina , Presedo Natalie , Harish Keerthi , Maldonado Thomas , Rhamkhelawon Bhama
Published: December 2023

Introduction:
Persistent endoleak and associated endotension following endovascular abdominal aortic aneurysm repair (EVAR) can compromise successful repair and lead to continued sac expansion and eventual life-threatening rupture event.

Hypothesis:
A risk-stratification algorithm of the inherent anatomical and systemic cellular characteristics of patients might predict the incidence of type II endoleaks on abdominal aortic aneurysm (AAA) patients undergoing EVAR or fenestrated endovascular aortic aneurysm repair (FEVAR) procedures.

Methods:
Single-center retrospective study includes 146 AAA patients undergoing primary elective EVAR and FEVAR procedures between September 2013 and July 2021. A review of institutional medical records was conducted for the analysis. Patients who or who did not developed a type II endoleaks were included in this study.

Results:
Mean platelet volume (MPV) was significantly increased in patients with type II endoleaks and was associated with lower endoleak-free survival. Receiver operating characteristic (ROC) curve analysis showed that MPV demonstrated satisfactory predictive performance in distinguishing patients who developed type II endoleaks, yielding an area under the curve (AUC) value of 0.64. A risk-stratification panel consisting of postoperative MPV, history of type II diabetes, and number of preoperative patent lumbar arteries achieved an AUC value of 0.72 and predicted endoleak-free survival rate with HR of 4.88. We built an easy-to-use nomogram for predicting the risk of postoperative type II endoleak and revealed that MPV had the highest scoring weight of any variable in our model.

Conclusions:
We refined the anatomical and systemic traits in the blood that identified MPV as a significant predictor for type II endoleaks, which might facilitate post-surgical monitoring using complete blood count (CBC) as a supplement to imaging practice.
Abstract 14527: AI-ECG is a Cost-Effective Early Screening Tool for Heart Failure With Reduced Ejection Fraction
Authors: Pawlowski Colin , Sobiesk Matthew , Hegstrom Lars , Rincon-Hekking John , Lopez-Jimenez Francisco , Kapa Suraj , Attia Zachi , Friedman Paul , Ardhanari Sankar , Barve Rakesh , Soundararajan Venky , Awasthi Samir
Published: December 2023

Background:
Early diagnosis of heart failure with reduced ejection fraction (HFrEF) can lead to reduced healthcare costs and improved outcomes. In this study, we evaluated the economic effectiveness of an AI algorithm for detecting low ejection fraction using 12-lead ECG data.

Aims:
The primary aim was to estimate the health economic impact of the AI-ECG algorithm intervention to detect low ejection fraction.

Methods:
The study population consisted of 113,719 individuals without a prior history of HFrEF who visited a multistate health system between 2010-2018 with 12-lead ECG data and an echocardiogram within 1 year. The AI-ECG algorithm was run retrospectively, and projected costs were estimated assuming each patient incurred the average cost based on their age group and AI-detected heart failure stage. Hospitalization costs were estimated using Medicare reimbursement rates, and economic benefits from increased survival were estimated using a willingness to pay of $50,000 per quality-adjusted life year (QALY) gained.

Results:
At the optimal model threshold, the total cost savings per patient (including benefits from QALYs gained) for the AI-ECG algorithm vs. standard-of-care on the overall study population were projected to be $79.11 (95% CI: [$53.77, $104.44]) and $124.93 (95% CI: [$83.99, $165.88]) for the 2 and 4 year periods, respectively. For patients over 50 years old, the projected total cost savings were $85.56 (95% CI: [$56.35, $114.78]) and $135.28 (95% CI: [$88.18, $182.38]) per patient for the 2 and 4 year periods, respectively. See Figure.

Conclusions:
The AI-ECG algorithm to detect low ejection fraction is a cost-effective early screening tool for HFrEF.
Abstract 14549: Body Mass Index Shift and Associated Cardiometabolic Risk Factors in People With Obesity or Overweight: A Post Hoc Analysis From SURMOUNT-1
Authors: Sattar Naveed , Srinath Reshmi , He Xuanyao , Falcon Beverly L , Lee Clare J , Stefanski Adam , Plat Arian
Published: December 2023

Introduction:
In SURMOUNT-1, treatment with once weekly GIP and GLP-1 receptor agonist tirzepatide resulted in substantial body weight reductions in people living with obesity.

Hypothesis:
This post hoc analysis assessed whether participants with obesity (body mass index [BMI] ≥30 kg/m
2
) or overweight (BMI ≥27 kg/m
2
with at least one weight-related comorbid condition) who shifted to a lower BMI category had improved cardiometabolic factors.

Methods:
Change in BMI category (<25 kg/m
2
, 25 to <30 kg/m
2
, 30 to <35 kg/m
2
, 35 to <40 kg/m
2
, and ≥40 kg/m
2
) from baseline to week 72 was assessed in participants from SURMOUNT-1 (N=2539) treated with tirzepatide or placebo. BMI shifts were grouped into “improved” (shift to at least one lower BMI category) or “stable” (no change) or “worse” (shift to a higher BMI category). Cardiometabolic parameters included waist circumference, fasting insulin, fasting glucose, HbA1c, blood pressure, and lipid profile.

Results:
In SURMOUNT-1, most participants demonstrated improved BMI with tirzepatide treatment (N=1457, 76.8%) while some had stable BMI (N=422, 22.3%) or worsened BMI (N=5, 0.3%) (Table). Furthermore, 38.1% improved by ≥2 BMI categories. Most placebo-treated participants had stable BMI. Compared to those with stable or worsened BMI, participants with improved BMI demonstrated greater improvement in cardiometabolic risk factors, including decreases from baseline in waist circumference, fasting insulin, fasting glucose, HbA1c, systolic and diastolic blood pressure, triglycerides, and cholesterol (non-HDL-c, and LDL-c) and increases from baseline in HDL-c.

Conclusions:
Substantial shifts to lower BMI categories were observed among tirzepatide-treated people living with obesity or overweight in SURMOUNT-1. Improved BMI and accompanying cardiometabolic risk factors with tirzepatide may lower further cardiovascular outcomes. Relevant outcomes trials are ongoing.
Abstract 14558: Causes and Predictors of Short-Term Readmissions Following Percutaneous Left Atrial Appendage Closure Procedure in Patients With and Without Rheumatic Mitral Valve Disease
Authors: Battikh Naim , Vardar Ufuk , Harb Ahmad , Vij Aviral
Published: December 2023

Introduction:
Atrial fibrillation (AF) is the most common cardiac arrhythmia, characterized by erratic heart beats. AF increases the risk of thromboembolic events particularly stroke. Percutaneous left atrial appendage closure (LAAC) is an alternative option to prevent embolic stroke in patients with AF who have contraindication to anticoagulants. Up to our knowledge, this is the first National Readmission Database (NRD) study to elucidate the difference in readmission rates between rheumatic vs non-rheumatic AF patients who underwent LAAC.

Methods:
We utilized the Nationwide Readmissions Database (NRD) between the years 2016-2020. The study involved hospitalizations with rheumatic mitral valve disease (R-MVD) and non-rheumatic mitral valve disease (NR-MVD) who underwent LAAC using ICD-10 diagnostic codes. We deemed this as the index admission. We excluded patients less than 18 years old and October-December hospitalizations from 90-day readmission analysis, due to lack of adjoining period to assess readmission.

Results:
Among 9,150 patients with mitral valve disease who underwent LAAC in their index hospitalizations, 9,122 were discharged alive. 4,200 patients (45.8%) were readmitted in 90-days. R-MVD 90-day readmission rate compared to NR-MVD (52.3% vs 40.7% respectively, p<0.001). The most common cause of readmission in both groups was atrial fibrillation, 96% of total readmissions in R-MVD and 97% of total readmissions in NR-MVD group. This was followed by “accidental puncture and laceration of a digestive system organ or structure” in 0.3% of R-MVD group vs “mitral valve insufficiency” in 0.7% of NR-MVD readmission causes. Figure 1 shows the Forest plot of multivariate analysis of independent factors associated with readmissions.

Conclusion:
Among AF patients who underwent LAAC with or without history of mitral valve rheumatic heart disease, those with history of R-MVD had significantly higher 90-day readmission rate.
Abstract 14572: Polypharmacy and Major Adverse Events in Atrial Fibrillation: Observations From the Korea National Health Insurance Service Data
Authors: Kim Hongju , Yang Pil-sung , Kim Daehoon , Sung Jung–Hoon , Yu Hee Tae , Kim Tae-Hoon , Pak Hui-Nam , LEE Moon Hyoung , JOUNG BOYOUNG
Published: December 2023

Introduction:
Previous evidence suggests that atrial fibrillation (AF) patients who receive polypharmacy are at an increased risk of experiencing adverse events. In this study, we investigated the prevalence of polypharmacy, identified risk factors associated with polypharmacy, and assessed the impact of polypharmacy on clinical outcomes in a ‘real-world’ data.

Methods:
We included 451,368 participants without AF (54[48.0-63.0] years; 207,748[46.0%] female) in the Korea National Health Insurance Service-Health Screening (NHIS-HealS) cohort from 2002 to 2013. All concomitant drugs were carefully collected and recorded. Polypharmacy was defined as the intake of ≥5 concomitant drugs. All-cause death, ischemic strokes/transient ischemic attacks (TIAs), major bleeding, heart failure admission were recorded.

Results:
With up to 7.7 (6.8-8.3) years of follow-up and 768,306 person-years, 12,241 incident AF cases occurred. Among included AF patients (40.0% females, 63.0[54.0-70.0] years), the prevalence of polypharmacy was 30.9 % (3,784). In new-onset AF, older age (per 10 increases, OR 1.32, 95% CI 1.26-1.40), hypertension (OR 4.00, 95 % CI 3.62-4.43), diabetes mellitus (OR 3.25, 95 % CI 2.86-3.70), COPD (OR 3.00, 95% CI 2.51-3.57), ischemic stroke/TIA (OR 2.36, 95% CI 2.03-2.73), dementia (OR 2.30, 95% CI 1.06-4.98), ESRD or CKD (OR 1.97, 95% CI 1.38-2.82), and heart failure (OR 1.95, 95% CI 1.69-2.26) were independently associated to the polypharmacy. Patients with polypharmacy showed significantly higher incidence and risk of major bleeding (aHR 1.26, 95% CI 1.12-1.41). All-cause mortality showed higher incidence, the risk was higher but not statistically significant (aHR 1.11, 95 % CI 0.99-1.24). The risks of stroke and heart failure admission were not changed by polypharmacy.

Conclusions:
In this “real world” nationwide AF cohort, polypharmacy was highly prevalent and conditioned worse prognosis due to its association with major bleeding events.
Abstract 14573: Dissecting Genetic Determinants Underlying Cardioskeletal Phenotypes Induced by Myopalladin Mutation in Murine Genetic Reference Population of Hybrid BXD Strains
Authors: Orgil Buyan-Ochir , Xu Fuyi , Alberson Neely , Stecchi Nathan , Martinez Hugo , Johnson Jason N , Lu Lu , Towbin Jeffrey A , Purevjav Enkhsaikhan
Published: December 2023

Introduction:
Mutations in myopalladin (
MYPN)
gene are associated with cardiomyopathies (CM) and skeletal myopathies (SM). This study is aimed to identify
Mypn
-induced cardioskeletal phenotypes in a murine genetic reference population (GRP) and uncover common genetic mechanisms underlying the development of CM and SM.

Hypothesis:
Mypn
induces common molecular signaling in cardiac and skeletal muscles.

Methods:
Pearson correlation between cardiac function and expression of Mypn in gastrocnemius muscles was performed in 40 mouse BXD recombinant inbred strains derived from C57BL/6J and DBA/2J parental mice. A causal Mypn-Q526X mutation was introduced to BXDs by crossing with MypnWT/Q526X knock-in mice and this generated F1 hybrid mutant (BXDQ526X) and wild type (BXDWT) strains. Cardiac (morphology, function by echo) and skeletal muscle (muscle mass, strength) phenotypes and transcriptomics (RNA-seq) were assessed in 3- and 6-month-old hybrid mice (N=5).

Results:
Skeletal muscle expression of
Mypn
was significantly associated with heart rate (HR) and heart mass (HM) in BXDs, while it was negatively associated with interventricular septum (IVS) thickness, indicating BXD strains with higher skeletal muscle
Mypn
expression had faster HR, higher HM but thinner IVS. Varied phenotypes in ejection fraction (EF%), ventricular volume and hypertrophy were found among BXD
Q526X
mice; BXD51
Q526X
, BXD48
Q526X
and BXD69
Q526X
strains had significantly higher EF%, while some mutant mice showed EF% decrease compared to their respective BXD
WT
littermates. Many mutant lines displayed significantly reduced skeletal muscle strength or mass. Overt SM-related signs (rear limb deformity, restricted movement, waddling) were seen in BXD78
Q526X
, while we found overlapping CM/SM traits in BXD51
Q526X
mice.

Conclusions:
In this study, common
Mypn
-induced molecular signaling in cardiac and skeletal muscles is identified. Introduction of the
Mypn
-Q526X mutation into the diverse genetic background of BXD GRP exposed CM- and SM-related phenotypes in hybrid lines. The most susceptible lines with overt and overlapping CM/SM phenotypes will be useful to identify common genes, networks and pathways involved in CM and SM using systems genetics methods.
Abstract 14596: Differences in Healthcare Resource Utilization Among Patients Receiving Comprehensive Guideline-Directed Medical Therapy by Prior History of Worsening Heart Failure Events
Authors: Coyle Catelyn R , Ru Boshu , Ambrosy Andrew P , McMullan Ciaran J , Stevenson Andra S , Ai Lei , Bash Lori D , Gaggin Hanna K
Published: December 2023

Background:
Heart failure (HF) is a leading cause of hospitalizations in the US. While Guideline-Directed Medical Therapy (GDMT) improves outcomes in patients with heart failure with reduced ejection (HFrEF), healthcare resource utilization (HCRU) among patients with worsening heart failure (WHF) has not been well characterized.

Aim:
We compare HCRU by history of WHF at initiation of “2022 GDMT” (i.e., ARNi+β-blocker+MRA+SGLT2i).

Methods:
Patients with HFrEF who had concurrent exposure for ARNi, SGLT2i, β-blocker, and MRA between Jan 2020-Jun 2022 were identified using Optum’s deidentified Clinformatics® Data Mart Database. HCRU (i.e., all-cause hospitalizations [ACH] and HF hospitalizations [HFH]) was compared by history of WHF (i.e., HFH or IV diuretic administration) in the prior 12 months. Cox proportional hazard and negative binomial regressions estimated factors independently associated with risk of first and recurrent hospitalizations and their durations, respectively.

Results:
The analytical cohort included 3,881 HFrEF patients receiving 2022 GDMT, 1,835 (47%) with a prior history of WHF. Patients with and without a history of WHF had similar sociodemographic characteristics. The median (IQR) follow-up time was 352 (244, 544) days for the cohort. Patients with WHF were hospitalized sooner, more frequently, and for a longer duration of time (
Table
) compared to those without. After adjusting for sociodemographic characteristics, WHF was independently associated with longer length of stay of ACH (coefficient, 95% CI: 1.91, 1.59-2.31) and HFH (2.13, 1.74-2.61) and almost three times the risk of first and recurrent ACH (HR, 95% CI: 2.93, 2.64-3.26) and HFH (2.93, 2.61-3.29).

Conclusion:
Prior history of WHF was associated with clinically meaningful and statistically significant worse HCRU, despite first-line “2022 GDMT”. Additional care strategies and novel therapies are required to further decrease residual risk among these patients.
Abstract 14620: Association of Rural Residence With In-Hospital Mortality for Heart Failure Hospitalizations in Texas: A Population-Based Cohort Study
Authors: Al-Ayyubi Rami , Qudrat Ullah Muhammad , Mata Andres , Gonzalez Reyes Laura , Parepalli Divya , Malik Muhammad Jehangir , Sanivarapu Raghavendra , Garza John
Published: December 2023

Background:
Rural residents with heart failure may be at higher risk of mortality due to disparities in access to health care services. Patterns of urban-rural disparity in health care resources may vary across the United States and population level analyses of the impact of rural residence on hospitalized patients with heart failure in Texas are not conclusive.

Hypothesis:
Rural residence is associated with increased risk of in-hospital mortality in patients with heart failure.

Methods:
We used publicly available, statewide, and deidentified hospitalization records to study patients aged ≥18 years with heart failure as principal diagnosis in Texas for years 2016 through 2021. Three models estimated the association between rural residence and in-hospital mortality. Multilevel logistic regression with propensity adjustment was the primary analysis approach with propensity score matching and multivariable logistic regression without propensity score matching applied as alternative analyses. Additional analyses were completed for patient subgroups and for categories of heart failures.

Results:
Out of 460,798 heart failure hospitalizations (HFH), 61,480 (13.3%) were classified as rural residents. HFH with
vs
without rural residence were older (70.4%
vs
64.8% aged ≥ 65years), more often white (63.5%
vs
46.9%), less frequently had private insurance (26.2%
vs
35.4%) and were less often admitted to teaching hospitals (19.5%
vs
28.9%); p < 0.0001 for each. Unadjusted in-hospital mortality among HFH with and without rural residence was 2.5%
vs
2.1%. On adjusted analyses, rural residence remained associated with higher odds of in-hospital mortality (adjusted odds ratio 1.1685 (95% CI [1.0878 - 1.2554]). The results were similar for the alternative modeling approaches, subgroup analyses, and categories of heart failures.

Conclusions:
Rural residence in Texas was associated with higher risk of in-hospital mortality in patients with heart failure.
Abstract 14627: Machine Learning Based Models for Imputing Heart Failure on First Medical Contact From the Get With The Guidelines®- Coronary Artery Disease (GWTG-CAD) Registry
Authors: Hong Haoyun , Poudel Remy , Li Shen , Thomas Kathie , Osho Asishana , Goyal Abhinav , Hall Jennifer L , Zhao Juan
Published: December 2023

Introduction:
The American Heart Association Get With the Guidelines - Coronary Artery Disease (GWTG-CAD) Registry is a quality improvement program with over 2600 participating U.S. hospitals. Among the collected data elements is the yes-no variable “Heart failure documented on First Medical Contact” (HF-FMC), an important clinical predictor of in-hospital mortality. Before 2018, the missing rate of HF-FMC exceeded 60% in some years, significantly limiting its utility as a predictor of in-hospitality mortality. We compared machine learning (ML)-based with traditional statistical methods to accurately impute missing HF-FMC values.

Methods:
We utilized admission records from the GWTG CAD Registry data from 2018 to 2021, including both STEMI and NSTEMI patients. We removed missing HF-FMC, using complete data as ground truth. The data was split into training and test datasets in a 3:1 ratio. Imputation was framed as a prediction task. For evaluation, we masked HF-FMC in the test set and compared the imputed values against the ground truth. For traditional methods, mode imputation, K-nearest neighbor imputer (KNN), and Multiple Imputation by Chained Equations (MICE) were applied. For ML models, we applied logistic regression, random forest and XGBoost. Shapley Additive exPlanations (SHAP) values were utilized to identify key features contributing to the ML models.

Results:
The study included 223,074 individuals (12.2% HF-FMC = “yes”), with mean (SD) age 64.9 (13.4) years (33.8% Female; and 77.3% White and 13.8% Black). Machine Learning models achieved higher AUROC scores compared to traditional models in imputing HF-FMC (Table 1). Top features for predicting HF-FMC are shown (Figure 1).

Conclusions:
Machine learning models outperformed traditional methods in imputing missing HF-FMC, a critical predictor of in-hospital mortality. SHAP values can identify key features in imputing clinically important variables with high degree of missingness.
Abstract 14628: Residual Stroke Risk Among Atrial Fibrillation Patients Treated With Warfarin or Novel Oral Anticoagulants: A Patient Level Meta-Analysis From Combine AF
Authors: Johnson Linda S , Benz Alexander P , Eikelboom John W , Wallentin Lars C , Patel Manesh R , Connolly Stuart , Healey Jeff S
Published: December 2023

Introduction:
Despite oral anticoagulation treatment atrial fibrillation (AF) patients have residual risk of ischemic stroke and systemic embolism (SE) which could potentially be mitigated.

Methods:
Harmonized individual patient data from five landmark trials testing direct oral anticoagulants (DOAC) were pooled in the COMBINE-AF dataset, which we used to calculate annual rate of ischemic stroke/SE according to CHA
2
DS
2
-Vasc score, history of stroke, and AF type.

Results:
We included 71,794 subjects (median age 72 IQR 65-78 years 61.3% male) with CHA
2
DS
2
-Vasc scores≥2 randomized to either standard- or lower-dose DOAC or warfarin, and followed for a median of 2.1 (IQR 1.5-2.7) years. The median CHA
2
DS
2
-VASc score was 4 (IQR 3-5), and 18.8% had a history of stroke and 76.4% had non-paroxysmal AF. The overall annual stroke/SE rate was 1.33%/year (95%CI 1.27-1.39%). Subjects with non-paroxysmal AF had higher stroke/SE rates, 1.38%/year (95%CI 1.31-1.45%) compared to 1.15%/year (95%CI 1.05-1.27%) with paroxysmal AF. The rate increased by a RR 1.36 (95%CI 1.32-1.41%) per CHA
2
DS
2
-VASc point; in subjects with CHA
2
DS
2
-VASc≥4, the stroke/SE rate was 1.67%/year (95%CI 1.59-1.75%). Annual stroke/SE rates were higher in subjects with a prior stroke, 2.51%/year (95%CI 2.33-2.71%), and increased with higher CHA
2
DS
2
-VaSc score; RR 1.11 (95%CI 1.05-1.18),
Figure 1
. After premature permanent discontinuation of study drug, which occurred in 22% of individuals, stroke/SE rates were 3.6%/year (95%CI 3.4-3.9%) overall; 6.5%/year (95%CI 5.7-7.4%) in those with prior stroke. During follow-up 8.9% of subjects died.

Conclusions:
Despite treatment with oral anticoagulation in a clinical trial setting, there remains an 8.4% risk of stroke/SE over five years in subjects with CHA
2
DS
2
-Vasc≥4, and 12.5% over five years in subjects with a prior stroke. Permanent discontinuation is common, and associated with stroke/SE risks of almost 20% over five years.
Abstract 14631: A Perfect Storm: Alcoholic Cardiomyopathy, Influenza B and the Battle Against Biventricular Thrombi and Pulmonary Embolism
Authors: Mirza Noreen , Rayad Mohammad Nabil , Gandhi Darshan , Farouji Iyad , Ahmed Eyad , suleiman Addi
Published: December 2023

Introduction:
Biventricular thrombi (BT) are a rare occurrence in clinical practice and when they occur in alcoholic dilated cardiomyopathy (ADCM), they are a complication of this condition. Secondary predisposing conditions that can promote thrombus formation include infections like Influenza B. Herein, we report a rare case of ADCM and influenza B propagating the development of biventricular thrombi and pulmonary embolism.

Case Presentation:
A 47-year-old healthy gentleman with a history of tobacco, marujuana and alcohol abuse presented with shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, non-productive cough, fevers and bilateral lower extremity swelling. Initial vitals were significant for tachycardia and slightly elevated blood pressure. On examination, the patient had decreased breath sounds in the right lower lobe with rales and trace lower extremity edema. Initial labs revealed elevated BNP, High-sensitivity troponin and d-dimer. Rapid influenza B was positive. Chest x-ray showed pleural effusion and CT angiogram chest revealed filling defect in the segmental and subsegmental branches of the right pulmonary artery. Echocardiogram revealed biventricular thrombi and LVEF of 10-15% with global LV hypokinesis. He was treated with oseltamivir, enoxaparin and was started on guideline directed medical therapy.

Discussion:
BT formation can occur in heart failure with reduced ejection fraction. ADCM induces LV dilation which creates a stagnant environment conducive to thrombus development. Influenza B can cause a prothrombotic state due to endovascular injury by proinflammatory mediators. Due to advanced diagnostic techniques, the incidence of BT has increased however, they remain a significant challenge due to embolization risks. This is the first case that highlights that patients with ADCM in combination with influenza B are predisposed to hypercoagulable states inducing fatal BT formation thus, prompt recognition is vital.
Abstract 14635: Prognostic Value of Heart Rate Variability in Black Americans: The Jackson Heart Study
Authors: Usman Muhammad Shariq , Salman Ali , Greene Stephen J , Starks Monique A , Sohail Muhammad Umer , Frazier-Mills Camille , Wu Hau-Tieng , Dinh Wilfried , Mentz Robert J , Butler Javed , Fudim Marat , Khan Mohammad
Published: December 2023

Background:
The prognostic value of heart rate variability (HRV) in Black Americans (BAs), who have distinct cardiac risk profiles, is not well studied. We aimed to investigate the association between HRV, all-cause mortality, and cardiovascular events in the Jackson Heart Study (JHS).

Methods:
We analyzed data from JHS participants who had HRV readings at baseline (2000-2004). HRV was measured as the standard deviation between subsequent R-waves on a 12-lead EKG. Data were analyzed up to December 31, 2014. Outcomes of interest were all-cause mortality and cardiovascular events (composite of incident stroke and coronary heart disease). Cox regression models were used to estimate hazard ratios (HRs) for the hazard of events in participants with an HRV below the median versus those with an HRV above the median. Restricted cubic splines (RCS) were used to explore non-linear interactions. All analyses were adjusted for age, sex, smoking, clinically relevant comorbidities, and risk factors.

Results:
Among the 3627 participants (mean age: 55.1 years; female: 62.4%), the median [IQR] HRV was 22.3ms [13.7, 36.1]. At baseline, participants with HRV below the median had a higher prevalence of several cardiometabolic diseases. Adjusted Cox regression showed that HRV below the median was associated with a 32% increased hazard of all-cause mortality (HR: 1.32 [1.09, 1.60]; P = 0.005) and a non-significant increase in incident cardiovascular events (HR: 1.28 [0.99, 1.66]; P = 0.059);
Figure 1A
. RCS suggested HRV has a non-linear relationship with all-cause mortality (P-nonlinearity: 0.0076) and cardiovascular events (P-nonlinearity: 0.0162), with the hazard of events beginning to increase sharply at HRV <25ms (
Figure 1B
).

Conclusion:
BAs had a higher mortality hazard associated with lower HRV readings, specifically <25ms. Consumer wearable sensors commonly record HRV, and our findings suggest that HRV could serve as a practical prognostic tool for this population.
Abstract 14643: Coronary Spotty Calcification is Associated With a Higher Level of Plaque Vulnerability and Vascular Inflammation in Patients With Stable Angina
Authors: Fujimoto Daichi , Daisuke Kinoshita , Suzuki Keishi , Yuki Haruhito , Niida Takayuki , Dey Damini , Lee Hang , McNulty Iris , Kakuta Tsunekazu , Jang Ik-kyung
Published: December 2023

Background:
There is controversy on clinical implication of spotty calcification in the coronary arteries. Optical coherence tomography (OCT) enables detailed plaque characterization including features of plaque vulnerability. Pericoronary adipose tissue (PCAT) attenuation is a recently developed marker for perivascular inflammation.

Methods:
Patients with stable angina pectoris (SAP) who had both computed tomography angiography (CTA) and OCT prior to coronary intervention were included. They were classified into two groups: spotty calcification group (calcification arc <90°, length <4mm) and macro calcification group. Non-calcified plaques or plaques with mixed spotty and macro calcification were excluded. The OCT findings of the culprit lesion and PCAT attenuation of the culprit vessel were compared between the two groups.

Results:
Among 316 patients, 62 had spotty calcifications and 66 had macro calcification in the culprit lesion. The spotty calcification group showed a significantly higher prevalence of lipid rich plaque (91.9% vs. 74.2%, p=0.008; Figure A), greater mean lipid arc (183.1 vs. 150.5°, p=0.01), and a higher level of PCAT attenuation (-71.7 ± 7.68 vs. -74.9 ± 9.17 HU, p=0.03; Figure B), compared with the macro calcification group.

Conclusion:
Plaques with spotty calcification are associated with a higher prevalence of lipid-rich plaques and a higher level of perivascular inflammation, compared to those with macro calcification.
Abstract 14649: Artificial Intelligence Model Predicts Sudden Cardiac Arrest Manifesting With Pulseless Electrical Activity versus Ventricular Fibrillation
Authors: Holmstrom Lauri , Bednarski Bryan , Chugh Harpriya , Aziz Habiba , Pham Hoang Nhat , Sargsyan Arayik S , Uy-Evanado Audrey , Salvucci Angelo , Jui Jonathan , Reinier Kyndaron , Slomka Piotr J , Chugh Sumeet S
Published: December 2023

Introduction:
There is no specific treatment for sudden cardiac arrest (SCA) manifesting as pulseless electrical activity (PEA) and survival rates are low; unlike ventricular fibrillation (VF) which is treatable by defibrillation. The ability to distinguish individuals presenting with PEA-SCA versus VF-SCA has potential mechanistic and therapeutic importance, but access to the initial SCA rhythm has been a limiting factor.

Objectives:
We trained and tested an AI model to differentiate PEA-SCA vs. VF-SCA in a novel setting that allows for determination of the initial rhythm.

Methods:
A subgroup of SCAs are witnessed by emergency medical services (EMS) personnel with zero response time, thereby providing the true initial rhythm. The internal cohort consisted of 421 EMS-witnessed out-of-hospital SCAs with PEA or VF as the initial rhythm in the Portland, OR metro area. Using demographics and clinical variables, we trained and tested an extreme gradient boosting model to distinguish PEA-SCA vs. VF-SCA. External validation was performed in EMS-witnessed SCAs from Ventura, CA.

Results:
In the internal cohort, the AI model achieved an area under the operating curve (AUC) of 0.68 (95% CI 0.61-0.76). Model performance was similar in the external cohort, achieving an AUC of 0.72 (0.59-0.84). Anemia, older age, increased weight, and dyspnea as a warning symptom were the most important features of PEA-SCA; younger age, chest pain as a warning symptom and established coronary artery disease were important features associated with VF.

Conclusions:
The AI model identified novel features of PEA-SCA and could distinguish EMS-witnessed individuals presenting with PEA-SCA vs. VF-SCA.
Abstract 14657: p66Shc Mediates SUMO2-Induced Endothelial Dysfunction and ROS Production
Authors: KUMAR JITENDRA , Uppulapu Shravan kumar , Kumari Sujata , Sharma Kanika , Yadav Ravi P , Kumar Vikas , Kumar Santosh
Published: December 2023

Endothelial dysfunction is one of the earliest changes promoting vascular pathologies. Studies suggest that promoting sumoylation increases endothelial dysfunction and development of atherosclerotic plaque. We showed that overexpression of SUMO2 (one of the sumo isoforms) leads to impaired vasorelaxation. However, the molecular signaling is not well understood.P66Shc is an adaptor protein known to regulate vascular function. Studies in mice suggest that p66Shc impairs endothelial function via promoting oxidative stress. Mice with p66Shc knockout are protected against endothelial dysfunction due to hyperlipidemia, diabetes, and aging. Therefore, we asked if p66Shc mediates endothelial effects of SUMO2. We show that p66Shc is modified by SUMO2 and knockdown of p66Shc in endothelial cells inhibits SUMO2-induced reactive oxygen species production as well as inflammation. To identify the specific residue of p66Shc getting sumoylated, we generated recombinant p66Shc and SUMO2ylated it with a commercially available kit. Using mass spectroscopy, we identified that lysine-81 in CH2 domain of p66Shc is specifically modified by SUMO2. We also show that SUMO2-modificaiton of p66ShcK81 promotes oxidative activation (serine-36 phosphorylation) and mitochondrial translocation of p66Shc which are essential for ROS production. P66Shc non-sumoylatable at lysine 81 (p66ShcK81R) is resistant to SUMO2-induced serine-36 phosphorylation and mitochondrial translocation. To examine physiological significance of p66ShcK81-SUMO2, we generated a mouse model having knock in of p66ShcK81R. Using aortic rings from p66ShcK81R knock in and wild type mice, we show that overexpression of SUMO2 significantly impairs endothelium dependent relaxation in wild type mice aortic rings while aortic rings from p66ShcK81R knock are protected against it. Together, we demonstrate that SUMO2-p66Shc is a novel molecular signaling regulating vascular endothelial function.
Abstract 14662: What Factors Contribute to the Presence of Coronary Microvascular Dysfunction in Patients With Non-Obstructive Coronary Artery Disease?
Authors: Teragawa Hiroki , Oshita Chikage , Uchimura Yuko , Hashimoto Yu , Nomura Shuichi
Published: December 2023

Introduction:
In recent years, there has been growing interest in coronary microvascular dysfunction (CMD). Several risk factors have been discussed as causes of CMD, but there are still many unknowns.

Hypothesis:
In this study, we evaluated clinical risk factors for CMD in patients with chest pain with non-obstructive coronary artery disease (INOCA).

Methods:
Sixty-two patients who were able to undergo comprehensive coronary angiography at the time of chest pain screening were included in the study. Patients with a history of heart failure were excluded. Comprehensive angiography excluded patients with organic coronary artery stenosis (%stenosis>50%) and was performed with the spasm provocation test using acetylcholine (ACh) to induce coronary spasm and with a pressure wire to evaluate CMD. Positive coronary spasm was defined as the presence of usual chest pain or electrocardiographic changes and >90% coronary artery constriction on angiograms in response to ACh provocation. In addition, a coronary spasm within one section of the American Heart Association’s classification was defined as a focal spasm. CMD was defined as the presence of coronary flow reserve (CFR) < 2.0 or an index of microcirculatory resistance (IMR) ≥ 25 obtained from a pressure wire. The clinical background leading to CMD was investigated and evaluated by logistic analysis.

Results:
Of 62 patients with INOCA, 26 (42%) had CMD. The results are shown in the table.

Conclusions:
These results suggested that factors contributing to CMD in INOCA patients were diverse: women, smoking, focal spasm, and elevated NTproBNP level. It is necessary to identify the cause of CMD before treatment in such patients.
Abstract 14663: Machine Learning to Detect Pulmonary Hypertension at Point-of-Care
Authors: Bridges Charles R , Burton Timothy , Fathieh Farhad , Nemati Navid , Gillins Horace R , Shadforth Ian , Ramchandani Shyam , McLaughlin Vallerie
Published: December 2023

Introduction:
Pulmonary hypertension (PH) is defined by mean pulmonary arterial pressure (mPAP) of
≥
21 mmHg or
≥
25 mmHg by right heart catheterization (RHC), (2022 and 2015 ERS/ESC guidelines). Based on a recent meta-analysis, the sensitivity and specificity of transthoracic echocardiography (TTE) is 83% and 72% in the 59% of patients where tricuspid regurgitant velocity (TRV) is available.

Research Question:
Can we develop a point of care method to detect PH, based on cardiac orthogonal voltage gradient (OVG) signals and photoplethysmographic (PPG) signals?

Aim:
Using OVG and PPG signals from subjects evaluated with RHC or TTE (independent of TRV), we built a machine learned (ML) model that can identify subjects with PH with high accuracy.

Methods:
3298 features from PPG and OVG signals were reduced to 216 via univariate testing. ElasticNet and Random Forest models were developed using a coarse grid-search based on 5-fold cross-validation followed by a narrow search when the two algorithms were ensembled, performed on a naive set of subjects with confirmed PH (N=327, mPAP
≥
21 mmHg; N=252, mPAP
≥
25 mmHg) vs. subjects with high negative predictive value for absence of PH, i.e., meeting the 2022 ERS/ESC TTE guideline criteria for “Low Probability” of PH adjudicated by a core lab (N=204). The model prediction for the selected hyperparameters was generated for every subject using out-of-fold prediction.

Results:
Table 1 demonstrates strong performance across gender and PH subgroups. AUC for all PH/Pre-capillary PH based on the 2015 ERS/ESC guidelines is 0.92/0.95, sensitivity 90%/95% and specificity 75%/75%. Using the updated 2022 guidelines, AUC for all PH/Pre-capillary PH is 0.90/0.92, sensitivity 90%/93% and specificity 69%/69%.

Conclusion:
Clinically relevant performance using a ML algorithm based on non-invasive signals collected at point-of-care is achievable in the identification of PH (and specifically, Pre-capillary PH), not limited by availability of TRV.