bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14425: Improved Carcinoid Heart Disease Mortality Amid Persistent Race, Income, and Rural Disparities: Propensity Score and Machine Learning Guided Analysis of 55,910 Carcinoid Cases From 2016-2018
Authors: Monlezun Dominique , Hassan Saamir , Honan Kevin , Kim Jin wan , Halperin Daniel , Dasari Arvind , Yao James , Gregoric Igor , Cilingiroglu Mehmet , Marmagkiolis Konstantinos , Koutroumpakis Efstratios , Iliescu Cezar
Published: June 2023

Introduction:
It is unclear what the rates of carcinoid heart disease (CHD) diagnosis, disparities, and inpatient outcomes are.

Methods:
We performed the first nationally representative longitudinal analysis of the above using Machine Learning-augmented Propensity Score adjusted multivariable regression (ML-PSr) and the 2016-2018 National Inpatient Sample (NIS), the United States’ largest all-payer inpatient dataset. The propensity score was modified for the likelihood of developing malignant carcinoid tumor (MCT).

Results:
From 2016-2018 among 101,521,656 hospitalizations, 55,910 (0.05%) had a malignant carcinoid tumor (MCT), of whom 4,030 (7.20%) had CHD. The rate of CHD diagnosis remained largely stable from 2016 (18,900 [0.06%]) to 2017 (19,025 [0.05%]) to 2018 (17,985 [0.05%]). Patients with versus without CHD had significantly higher unadjusted mortality in 2016 (4.05% versus 2.19%), 2017 (3.75% versus 1.95%), and 2018 (3.75% versus 1.95%). Of patients with CHD, 0.15% had acute carcinoid syndrome. Compared to the racial distribution throughout the population, the diagnosis of CHD was under-represented in Hispanics (12.83% versus 7.95%), Asians (3.13% versus 2.84%), lowest income quartile (29.47% versus 28.07%), second lowest income quartile (26.90% versus 25.41%), metros of 250,000-999,999 residents (20.79% versus 19.73%) and metros of 50,000-249,999 (9.30% versus 8.56%) (all p<0.001). In ML-PS multivariable regression fully adjusting for age, sex, race, metro density, region, metastasis, and NIS calculated mortality risk by DRG, CHD initially significantly increased mortality in 2016 (OR 1.18, 95%CI 1.10-1.28; p<0001) but decreased it in 2017 (OR 0.76, 95%CI 0.70-0.82; p<0.001) and 2018 (OR 0.78, 95%CI 0.72-0.84; p<0.001). In ML-PSr stratified by income in 2018, there was largely a step wise decrease in mortality with CHD from the lowest income quartile to highest income quartile.

Conclusions:
Our analysis demonstrates that racial minorities, lower income, and more rural metros have lower rates of CHD diagnosis, its associated mortality appears to be the lowest with higher income, and its mortality over time across all patients in general appears to be decreasing potentially with improved inpatient care.
Abstract 14438: Longitudinal Real World Study of Blood Pressure and Cerebral Arterial Stenosis on Elderly Cognitive Impairment Based on the Artificial Intelligence Analysis of Serial Brain Magnetic Resonance Angiography
Authors: Sun Shasha , Xu Xian , Zhou Yanfeng , Cui Longbiao , Jiang Jiacheng , Fan Li , Cao Feng
Published: June 2023

Background:
Abnormal blood pressure (BP) is one of the most common modified risk factors for the development of cognitive impairment (CI) with increasing aging population.

Objective:
This study aims to investigate the association between risk factors and CI in elderly patients based on artificial intelligence (AI) analysis of BP measurements and brain magnetic resonance angiography (MRA).

Methods:
A total of 3221 elderly individuals undergone brain MRA were recruited into the nested case-control study from 2007 to 2021. Patients were divided into two groups according to diagnosis with or without CI. Data were collected before diagnosing CI. The stenosis rate of cerebral arteries was calculated by AI analysis of brain MRA. Four machine learning modalities were applied to establish predictive models.

Results:
A total of 416 cases (mean age 84.47 ± 6.50 years old) with or without CI were finally recruited into the study after matching with age and gender. Mean follow-up time was 3.46 ± 3.19 years. The number of BP measurements was 56.98 ± 77.94 times. In the univariate logistic regression model, high systolic blood pressure (SBP) (OR 1.029, 95% CIs 1.010-1.049), pulse pressure (PP) (OR 1.043, 95% CIs: 1.021-1.065) and pulse pressure index (PPI) (OR 3588.920, 95% CIs: 44.392-290148.336) increased the risk of CI. Based on various mean BP parameters, the predictive ability of the support vector machine (SVM) was improved after adding cerebral arterial stenosis rate (AUC 0.781, 95% CIs 0.639~0.923).

Conclusion:
Abnormal SBP, PP and PPI were risk factors for CI in the elderly Chinese population. Adding the cerebral arterial stenosis rate of internal carotid artery and posterior cerebral artery the predictive ability of SVM model of various mean BP parameters for the risk of CI was improved.
Abstract 14458: It Takes Three to Tango: A Case of Occult
Streptococcus Gordonii
Infectious Endocarditis After Dental Cleaning Identified by History, Multi-Modal Imaging, and a Multi-Disciplinary Effort
Authors: Tsay Annie J , Gavin Michael C , Datta Neil
Published: June 2023

Introduction:
We present a case of a 65 year-old man with severe aortic regurgitation requiring a stented 23mm Edwards bioprosthetic aortic valve (BioAVR), who presented with 3-months of fevers and fatigue found to have
Streptococcus gordonii
(
S. gordonii
) infectious endocarditis (IE). He underwent dental cleaning 3-months prior sans prophylactic antibiotics. An echocardiogram on admission revealed increased peak/mean systolic gradients across the BioAVR to 46/26mmHg compared to gradients one year prior (32/19mmHg). Initially, a vegetation was not visualized by transthoracic echocardiogram (TTE) despite radiographic evidence of multi-organ emboli. Serial TTEs and transesophageal echocardiograms (TEEs) were performed due to persistent symptoms. Eventually, a new vegetation was visualized by TEE. A team effort involving cardiology, infectious disease, neurology, and cardiac surgery was required for management. Revision of the BioAVR was not pursued due to resolution of the vegetation. The patient was discharged after a prolonged hospitalization with recommendations to take amoxicillin 2g prior to future dental work.

Results:
Figure 1. A new 0.5cm vegetation visualized by TEE (A) with enlargement to 0.8cm (B), followed by a healed vegetation (C), and resolution 7-months later.

Conclusions:
S. gordonii
has historically been a rare cause of IE therefore requiring a high clinical suspicion for diagnosis. Approximately 8% of IE cases are caused by streptococci. However, a recent study in Denmark on streptococci IE implicated
S. gordonii
in 44.2% of IE cases
. S. gordonii
is a gram-positive cocci found in oral flora known to cause subacute bacterial endocarditis. Our case highlights the importance of detailed history-taking to identify sources of infection, serial multi-modal imaging evaluation despite initial negative findings particularly with persistent clinical symptoms, and a multidisciplinary approach to IE cases due to multi-organ involvement.
Abstract 14460: Aortic Valve Infective Endocarditis Complicated by Complete Heart Block and Gerbode’s Defect
Authors: Ahmad Soban , Pandya Dishita , Ardhanari Sivakumar
Published: June 2023

Introduction:
Aortic root abscess with complete heart block is a rare complication of infective endocarditis (IE). Early diagnosis and prompt surgical management are necessary to prevent fatal outcomes.
Case Presentation:
A 45-year-old male with past medical history of uncontrolled diabetes mellitus was referred to our cardiac intensive care unit for management of complete heart block. His symptoms including exertional dyspnea, hiccups, and dry cough started two weeks prior to presentation. The patient was bradycardic, hypoxic, and hypotensive on examination. Labs were significant for marked leukocytosis 21,000/ul with a neutrophilic predominance. Blood cultures were obtained, and the patient was started on empiric antibiotics vancomycin and piperacillin-tazobactam. Electrocardiogram (ECG) showed evidence of complete heart block and a temporary transvenous pacemaker was placed. A transthoracic echocardiogram was obtained that showed evidence of severe aortic regurgitation and aortic valve vegetations. Due to high clinical suspicion, a transesophageal echocardiogram was immediately performed that revealed aortic root abscess. Patient underwent successful debridement of aortic valve vegetations and aortic valve replacement. Intraoperative findings also included a subaortic left ventricular to right atrial (LV-RA) shunt also known as Gerbode’s defect that was repaired with pericardial patch. Blood cultures and intraoperative tissue cultures confirmed a Staphylococcus lugdunensis infection. He received six weeks of intravenous antibiotics. At 2-month follow-up, the patient reported doing well.

Conclusion:
New complete heart block may be a manifestation of aortic root abscess. This case illustrates the need to maintain a high level of suspicion for complicated infective endocarditis in patients with sepsis and complete heart block. Timely diagnosis with imaging and early surgical repair results in favorable outcomes.
Abstract 14462: Diversity of Cardiology Fellowship Candidates in the Era of Virtual Interviews
Authors: Witting Celeste , Gummidipundi Santosh E , Heidenreich Paul A , Knowles Josh , Yong Celina M
Published: June 2023

Introduction:

The goal of cardiovascular training programs is to increase recruitment of women and underrepresented in medicine (UIM) trainees. Due to the COVID-19 pandemic, virtual interviewing replaced in-person interviewing for cardiology fellowship applications in the United States. However, there is little data on the influence of these changes on fellowship candidate diversity.

Methods:
In a single-center retrospective study, we identified demographic changes in the profiles of trainees who interviewed for the Stanford University Cardiovascular Fellowship Program before and after the transition to virtual interviewing (2019 and 2020 vs 2021 and 2022 cycles). UIM applicants were defined as those who self-identified Black or Hispanic. Test of proportions and t-test were used for categorical and numeric variables respectively.

Results:
Over four years, 2250 trainees applied, 212 candidates interviewed, and 24 were accepted to the fellowship. Of those interviewed, 42.0% were women, 9.9% were Black, and 9.4% were Hispanic. The proportion of UIM trainees interviewed increased from 10.5% during the in-person years to 30.2% during the virtual years (p < 0.001; Figure 1A). The increase among women was not statistically significant (40% in-person vs. 44% virtual, p = 0.58). The geographic distribution shifted over time to include lower representation from closer Western programs (40% in-person to 29% virtual) and higher representation from Northeast programs (35% in-person to 44% virtual; Figure 1B). The weighted mean distance of represented residency programs nominally increased from 1730 miles to 2067 miles away (p = 0.06).

Conclusions:
Virtual interviews were associated with a three-fold increase in UIM interviewed applicants for cardiology fellowship positions at a single center. Further research is warranted to assess the full impact of virtual interviews, as well as to understand and mitigate potential bias in the evolving selection process.
Abstract 14522: Infective Mitral Valve Endocarditis in an Immunocompetent Patient Caused by Lactobacillus Species Transmitted by Intranasal Cocaine Use
Authors: Kolimas Amie M , Ajmal Muhammad , Avila Danielle D , Kotagiri Rajesh , Kazui Toshinobu , Moynahan Kevin J , Corban Michel T
Published: June 2023

A 59-year-old male with controlled DM2, HTN, tobacco abuse, and remote MSSA bacteremia secondary to longstanding intranasal cocaine use (never IV drug user) presented to the ER with acute onset of left leg pain. He was in extreme distress and examination showed a cold left leg with absent extremity pulses. Cardiac assessment was notable for an apical systolic murmur. Magnetic resonance angiography (MRA) of the leg revealed a thrombotic occlusion of the left common femoral artery extending into the popliteal artery prompting emergent successful femoral artery thrombectomy and compartment fasciotomy. An intraoperative TEE revealed mobile echodensities on the anterior and posterior MV leaflets with severe eccentric mitral regurgitation (MR) [Figure1]. Blood and thrombectomy debris cultures yielded
Lactobacillus acidophilus
vs.
gasseri
species. Further workup showed multiple small embolic infarcts on MRA head and chronic sinusitis on CT sinuses, while CT chest, abdomen and pelvis were unremarkable. He received IV ampicillin for 1 week with bacterial clearance, followed by bioprosthetic mitral valve replacement. Gram stain of the mitral valve revealed gram positive rods, cultures grew Lactobacillus species, and histopathology confirmed the presence of infective endocarditis. The patient completed 7 weeks of penicillin G intravenously with clinical recovery.
Lactobacillus acidophilus
and
gasseri
are normal flora of the human oral cavity, gastrointestinal and genitourinary tracts. Lactobacillus endocarditis is rare and has been identified in only 0.05-0.4% of endocarditis cases. Infections primarily affect the immunocompromised, but to the best of our knowledge this is the first case of Lactobacillus mitral valve endocarditis presenting with concomitant acute limb ischemia with infected thromboembolic debris in an immunocompetent individual with the suspected inciting event being intranasal cocaine use causing trauma to the nasal vasculature.
Abstract 14546: Long-Term Outcome of Immediate Aortic Repair for Acute Type A Aortic Dissection Complicated With Brain Malperfusion
Authors: Tsukube Takuro , Nakai Chikashi , Kanno Reiko , Sakaguchi Kazunori , Kondo Mayo , Izumi So
Published: June 2023

Introduction:
Management of acute type A aortic dissection complicated by brain malperfusion remains controversial. We previously reported an excellent recovery of consciousness for patients with coma if aortic repair performed within 5 hours from onset of symptoms. This study evaluates neurological outcomes after 19 years with this approach.

Methods:
Between 8/03 and 12/21, aortic repair was performed in 400 patients with acute type A aortic dissection, including 59 (12.7%) presented with brain malperfusion on arrival. Brain malperfusion was defined as distributed consciousness or paralysis in patients with dissection in carotid artery on hospital arrival. Forty patients (67.8 %) were repaired within 5 hours from onset of symptoms (immediate repair) while 19 (32.2 %) were repaired after 5 hours (later repair). We compared the immediate repair group with the later repair group. The mean age of the patients was 70.0±11.7 and 70.0±9.0 years, respectively, and prevalence of shock, cardiac tamponade, EuroSCORE were not significantly different between two groups. Preoperative coma (GCS<10) coexisted in 60.0 and 47.4%, respectively. For brain protection, deep hypothermia with antegrade cerebral perfusion was utilized. Glasgow Coma Scale (GCS) and modified Rankin Scale (mRS) were used for neurological evaluation.

Results:
Time from onset of symptoms to operating room was 3.4 ± 0.9 in immediate group and 14.2 ± 13.3 hours in later group. Total arch replacement was performed in 35.0 and 36.8%, respectively. Changes of GCS was significantly better in immediate group (p=0.03), and cut off value of time from onset to operating room for predicting consciousness recovery was 249minutes (p=0.02). Postoperative ADL independence (mRS<3) was achieved in 50.0% (20/40) and 36.4% (7/19), respectively. The follow-up periods were between 0.6 and 216 (mean 47.8) months. Cumulative survival rate in 10 years of immediate group was 63.4% and significantly better than that of later group (49.0%).

Conclusions:
Long-term outcomes following the strategy of immediate aortic repair for acute type A aortic dissection complicated by brain malperfusion were satisfactory.
Abstract 14580: Electrocardiographic Machine Learning to Identify Elite Endurance Male Athletes: Chief Heart Study
Authors: Lin Gen-Min
Published: June 2023

Background:
Several electrocardiographic (ECG) features have been identified for athlete’s heart. However, it is unknown whether using machine learning for ECG features could identify the elite athletes.

Methods:
In a large population of 2,296 physically active military males, aged 17-43 years, three machine learning classifiers including logistic regression (LR), multilayer perceptron (MLP), and support vector machine (SVM) for 26 ECG features (axis, duration and voltage of P, QRS and T waves in each lead) and 6 biological features (age, anthropometrics, blood pressure and pulse rate) were used to identify the elite athletes from the study population. Elite athletes were defined as those who had the top 10% performance in a 3000-meter run test (with a mean time of 747 sec) and the remaining 90% were as the control group (with a mean time of 871 sec). The data of the 2,296 participants were randomly grouped by a 3:1 ratio into a training/validation set (N =1,607) and a test set (N =689).

Results:
The area under the receiver operating characteristic curve (ROC) from the best to the worst performance of the three machine learning classifiers were listed in order: the LR (80.81%), followed by the MLP (78.43%), and the SVM (63.30%) (Figure 1). If the specificity is set around 70.0%, the sensitivity of the LR and MLP is estimated to 81.82%.

Conclusions:
This study suggests that it is feasible to utilize machine learning for ECG and biological features to identify the elite athletes. The proposed MLP and LR methods could provide acceptable detection ability for elite athletes and may be helpful to monitor the physical training status for athletes.
Abstract 14588: A Large-Scale Genome-Wide Association Study of Angiographically Determined Burden of Coronary Atherosclerosis in a Genetically Diverse Population
Authors: Hilliard Austin , Zanetti Daniela , lynch julie , Damrauer Scott M , Ho Yuk-lam , Plomondon Meg E , Waldo Stephen , Chang Kyong-Mi , Tsao Philip S , CLARKE Shoa L , Assimes Themistocles L
Published: June 2023

Introduction:
Few large-scale genome wide association studies (GWAS) of angiographically derived burden of coronary atherosclerosis have been reported to date. The yield of this approach relative to case-control GWAS of coronary artery disease (CAD) remains unclear.

Methods:
We used the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program, a national quality and safety organization for invasive cardiac procedures, to conduct the largest ever GWAS of burden of coronary atherosclerosis involving participants of the Million Veteran Program (MVP). Obstructive disease of a native major vessel was defined as the presence of at least one obstruction >50% of the luminal diameter, or a prior revascularization procedure, involving the main artery and/or its major branches. Non-obstructive disease was defined as one or more vessels having one or more obstructions of >20% but none more than 50%. We classified an individual’s extent of disease as normal, non-obstructive, one vessel, two vessel, or three vessel / left main CAD. GWAS was performed stratified by racial/ethnic group using linear regression in REGENIE, with age, sex, and genetic principal components as covariates. Stratified results were then combined through meta-analysis using GWAMA.

Results:
The extent of disease was quantified in 49,213 non-Hispanic White, 11,326 non-Hispanic Black, and 4,058 Hispanic MVP participants, a majority of which were subjects with clinical CAD. Forty-three loci reached genome wide significance including 27 among Whites, four among Blacks at
SORT1
,
LPL
,
COL4A2
, and
LDLR
, two among Hispanics at
CDKN2B-AS1
and
NRG4
, and an additional 13 through meta-analysis of all three strata. Two loci,
HHEX
and
NRG4
, have not been previously established as susceptibility loci CAD.

Conclusions:
Large-scale GWAS of burden of coronary atherosclerosis complements discovery efforts of case-control GWAS of CAD. Despite substantially smaller sample sizes, this quantitative approach recapitulated many established loci for CAD, uncovered novel loci, and identified several known susceptibility loci in admixed Black and Hispanic populations. The latter required a remarkably larger sample size to achieve through GWAS of clinically defined events alone.
Abstract 14606: Accurate Detection of Acute Psychological Stress Events Using Single Lead ECG Data
Authors: Deery Adrian , Lilburn Mark , McKenna Stacey , Fitzpatrick Matthew , Easlea Holly , Funston Rebecca , Condon Adrian , Mitchell Andrew R
Published: June 2023

Introduction:
Stress has been linked to numerous health conditions, including heart disease, diabetes, and mental health issues. By monitoring changes in physiological signals, such as heart rate (HR) and heart rate variability (HRV), wearable biosensing technology allows acute stress to be non-invasively tracked over long periods, providing valuable insights for preventative healthcare.

Methods:
This two-phase study comprised several protocols designed to induce varying levels of psychological stress in participants (N=39). HR and HRV metrics, derived from electrocardiogram (ECG) data collected throughout the protocol on the single lead HeartKey
®
Chest Module, were used by the HeartKey Stress algorithm to generate a relative stress score (0-100), which was validated against two clinically recognized methodologies for assessing patient stress: i) state-trait anxiety index (STAI), a questionnaire that subjectively measured the individual’s perceptual stress after each stage of the protocol, and ii) electrodermal activity (EDA), which continuously monitored conductive changes at the skin’s surface with an Empatica
®
E4 wrist wearable.

Results:
Over both phases, participant STAI scores increased significantly during stress protocols (49.9 ± 23.3) relative to the baseline (30.0 ± 10.0). Mean HR showed a similar significant increase (
p
< 0.001), and HRV gradually decreased throughout the testing protocol. HeartKey Stress scores derived from HR and HRV data showed a strong correlation to STAI scores. Furthermore, the HeartKey Stress trend closely replicated that of the EDA data.

Conclusions:
HeartKey Stress algorithm consistently generated accurate and reliable stress scores in response to events of induced, acute psychological stress. The results suggest that the algorithm has potential utility for continuous clinical monitoring of patients with stress-related illnesses.
Abstract 14618: Mitochondria-Rich Extracellular Vesicles From Stem Cell-Derived Cardiomyocytes Restore Cardiac Energy Metabolism of Ischemic Myocardium in a Preclinical Pig Model
Authors: Ikeda Gentaro , Takashima Hiroyuki , Zhao Chunli , Bayardo Nathan , lyins jennifer , O'Brien Connor , Yang Phillip C
Published: June 2023

Introduction:
Disruption of mitochondrial energy metabolism underlies the pathophysiology of heart failure. We previously demonstrated that intramyocardial injection of mitochondria-rich extracellular vesicles (M-EVs) from iPSC-derived cardiomyocytes (iCMs) transfer mitochondrial and nonmitochondrial substances into the recipient cardiomyocytes, stimulating mitochondrial biogenesis and functional capacities in the murine acute myocardial infarction (MI) model. However, the therapeutic potential and underlying mechanism in larger animal models remain to be assessed.

Methods:
M-EVs were isolated from the conditioned medium of iCMs via differential ultracentrifugation. Yorkshire pigs were subjected to myocardial ischemia for one hour via balloon occlusion of the left anterior descending artery. 1.0 x 10
11
M-EVs were injected into the infarct border zone using a percutaneous catheter delivery system (Biocardia, Inc). Cardiac functions were analyzed by cardiac MRI. Liquid chromatography-tandem mass spectrometry was performed to investigate comprehensive protein profiles of M-EV content and pig heart tissue samples.

Results:
Flow cytometric and electron microscopic analysis revealed that mitochondria inside M-EVs retained membrane potentials and structural integrities. M-EV therapy significantly improved left ventricular (LV) ejection fractions (30.5 vs. 21.2 %, p=0.004) and reduced LV end-diastolic volume (119 vs. 192 mL, p=0.047) at week-4 as compared with PBS control. No difference was observed in the scar size. Proteomics analysis identified a total of 37 significantly enriched proteins in M-EVs. Gene Set Enrichment Analysis of the M-EV proteome revealed significantly upregulated biological processes, including oxidative phosphorylation. STRING network analysis identified enriched proteins that directly or indirectly interact with a proliferator-activated receptor γ coactivator-1 α, a master regulator of mitochondrial biogenesis.

Conclusion:
M-EV-mediated transfer of mitochondria and enriched proteins enhanced cardiac function by restoring energy metabolism in pig acute MI model. M-EV therapy may represent a novel biologic that directly targets energy metabolism in mitochondria-related diseases.
Abstract 14644: The Association Between Neighborhood Distress and Outcomes Following Peripheral Vascular Intervention
Authors: Strand Eric , Smolderen Kim G , Romain Gaelle , Burg Matthew , Faridi Kamil , Churchwell Keith B , Mena-Hurtado Carlos
Published: June 2023

Introduction:
Peripheral arterial disease (PAD) is associated with an elevated risk of mortality. Low socioeconomic status (SES) is associated with increased prevalence and severity of PAD, and low SES has been associated with poor post procedural outcomes in cardiovascular disease. The Distressed Communities Index (DCI) uses seven common proxies of SES, such as educational attainment, housing stability, median income, and employment rate, to generate an aggregate score at a zip code level.

Hypothesis:
We hypothesized that increased levels of neighborhood distress, as measured by the DCI, is associated with an increased risk of mortality and amputation after PVI.

Methods :
We queried the Vascular Quality Initiatives (VQI) database, linked with Medicare claims data for patients who had undergone PVI. A total of 16,980 patients with PVI were found and 53 Excluded because ≥ 1 missing data for covariate used in modelling and 381 because DCI Missing. Patient 5-digit zip codes were used to obtain a DCI score (range 1-100, with higher scores indicating greater distress) from the Economic Innovation group. We examined the association between DCI and 2-year mortality and major amputation.

Results:
At 24 months, 2 964 (17.5%) had died 1 669 (9.9%) and had a major amputation DCI score was positively associated 2-year mortality risk. A 10-point higher DCI score was associated with increased mortality risk (unadjusted HR=1.02; 95%CI [1.01,1.03]) and a higher risk of amputation (unadjusted HR=1.05; 95%CI [1.04,1.07]). Fig.

Conclusions:
Higher level of community deprivation was associated with increased risk of short-and long-term mortality and amputation outcomes following PVI. PAD care pathways should integrate improved risk assessments and integrated care models for patients from distressed communities to help address health disparities.
Abstract 14699: Effect of Shear Stress on Arterial Inflammation and Development of Healed Plaque: A Comprehensive Shear Stress-Molecular Imaging Study Based on a Novel Multispectral Fluorescence Lifetime Imaging Catheter
Authors: Kim Sunwon , Nam Hyeong Soo , Kang Dong Oh , Han Jeongmoo , Yoo Hongki , Kim Jin W
Published: June 2023

Introduction and Hypothesis:
Endothelial shear stress (ESS) is the tangential force produced by luminal blood flow on arterial endothelium. Both high ESS and low ESS are known to have atherogenic effects, however, it remains poorly understood how these different forces influence coronary atherosclerosis. We evaluated the impact of ESS changes on biochemical and phenotypic difference of coronary atheroma, as assessed by a novel dual-modal optical coherence tomography-fluorescence lifetime imaging (OCT-FLIm)
in vivo
in beating human coronary arteries.

Methods and Results:
We constructed a fully-integrated OCT and multispectral FLIm system based on a low-profile dual-modal imaging catheter. High-speed OCT-FLIm could be performed safely in patients undergoing coronary revascularization (Pullback speed: 10-20mm/sec). 3D artery model for computational fluid dynamics was reconstructed by fusion of OCT and angiography. We analyzed spatial associations between ESS and multispectral FLIm information: ch.3(542nm) = fibroatheroma with inflammation; ch.1 (390nm) = loose fibrous tissue (healed plaque). OCT-FLIm visualized coronary microstructure clearly and offered correctly-coregistered biochemical readouts of coronary atherosclerotic plaque
in vivo
in a label-free manner. Fibroatheromas with increased inflammation activity, as assessed by ch.3 FLIm, were found in low ESS area. On the other hands, high ESS area colocalized with regions with increased ch.1 lifetime, a FLIm signature of loose fibrous tissue (healed plaque). Based on a coregistered ESS-FLIm data, we found a statistically significant negative correlation between ESS and ch.3 lifetime (p>0.001) and a positive correlation between ESS and ch.1 lifetime (p>0.001).

Conclusions:
Low ESS was associated with lipid and macrophage infiltration whereas high ESS was associated with presence of loose fibrous tissue, a histologic marker of recent plaque disruption leading to rapid plaque progression. Our novel imaging strategy enabling comprehensive evaluation of complex interaction between ESS and biochemical phenotype of plaques is expected to enhance understanding of coronary atherosclerosis biology.
Abstract 14707: Electrocardiographic Abnormalities Are Common in DCM Patients’ Family Members With Early Manifestations of DCM
Authors: Harris Chelsea S , Amar David , Howard Nicole E , Kinnamon Daniel D , Cao Jinwen , Ni Hanyu , Huggins Gordon S , Haas Garrie , Hershberger Ray E , Wheeler Matthew T
Published: June 2023

Introduction:
Imaging and 12-lead electrocardiogram (ECG) are recommended to screen individuals at risk of dilated cardiomyopathy (DCM). Few studies have examined the yield of ECG testing in these individuals. We hypothesized that ECG abnormalities are more frequent in DCM patients’ family members with early imaging manifestations of DCM than in those without.

Methods:
The multisite DCM Precision Medicine Study collected contemporaneous imaging and ECG in 1226 First Degree Relatives (FDRs) of DCM patients aged ≥ 18 years between 06/2016 and 04/2021. Imaging results were used to classify participants into four phenotype groups: left ventricular systolic dysfunction alone (LVSD), left ventricular enlargement alone (LVE), DCM (both LVSD and LVE), or normal (neither LVE nor LVSD). ECG status was defined as normal, borderline, or abnormal. Analysis of the probability of a borderline or abnormal ECG result was performed using a generalized linear mixed model accounting for clinical site heterogeneity and intrafamilial correlation.

Results:
Both imaging and ECG findings were normal in 57% of FDRs. ECG findings were abnormal or borderline in 42% of FDRs with LVSD or LVE and 87% of FDRs with DCM. As shown in Table, FDRs with DCM were more likely than FDRs with no LVE or LVSD to have abnormal or borderline ECGs after adjusting for race, ethnicity, age, sex, and family ascertainment site (OR: 13.17; 95% CI: 5.18 - 33.50). African American FDRs had higher adjusted odds of abnormal or borderline ECG findings than White FDRs (OR: 1.59; 95% CI: 1.15 - 2.20). FDRs in the 4th quartile by age had higher adjusted odds of abnormal or borderline ECG findings than FDRs in the 1st quartile (OR: 4.36; 95% CI: 3.01 - 6.33).

Conclusions:
An abnormal or borderline ECG was substantially more likely in at-risk FDRs who, by imaging, had DCM. This study supports the use of ECG testing in the screening of FDRs for DCM.
Abstract 14750: Mechanical Circulatory Support Devices Among Patients With Familial Dilated Cardiomyopathy
Authors: Shetty Naman S , Parcha Vibhu , Hasnie Ammar , Pandey Ambarish , Arora Garima , Arora Pankaj
Published: June 2023

Introduction:
With increasing disease recognition and widespread availability of genetic testing, it is important to characterize the clinical outcomes and prognosis among familial dilated cardiomyopathy (DCM) patients with stage D heart failure requiring a mechanical circulatory support device (MCSD). INTERMACS (INTEragency Registry for Mechanical Assisted Circulatory Devices) was examined to assess the clinical characteristics and outcomes of familial DCM patients who received an MCSD.

Methods:
DCM patients who received an MCSD between June 2005-December 2017 were classified according to their etiology. The primary outcome was death (with heart transplant as a competing risk) and the secondary outcome was heart transplant (with death as a competing risk). Multivariable-adjusted Cox regression analyses were used to assess the risk of study outcomes across DCM etiologies.

Results:
Among 19,928 DCM patients, 8,622 (43.3%), 7,091 (35.6%), 568 (2.9%), and 3,647 (18.3%) had ischemic DCM, idiopathic DCM, familial DCM, and DCM due to other causes respectively. Familial DCM patients had the lowest median age at implantation [46 (34, 56) years] compared with other DCM etiologies. Bridge to transplant was the most common device strategy (78.4%) in the familial DCM group (45.6% were listed and an additional 32.8% were eligible for a heart transplant). Familial DCM patients had the lowest adverse events of bleeding, device thrombosis, infection, and respiratory failure post-MCSD implantation. Over a median follow-up of 1.0 (0.4, 2.0) years, familial DCM patients had the lowest risk of death [HR
adj
: 0.68 (95% CI: 0.55-0.83)] and the highest likelihood of heart transplantation [HR
adj
: 1.47 (95% CI: 1.28-1.69)] compared with the other DCM groups.

Conclusions:
Among DCM patients receiving MCSDs, familial DCM patients had the lowest adverse events, the lowest risk of death, and the highest likelihood of heart transplantation, compared with other DCM etiologies.
Abstract 14758: Novel Deep Learning Algorithm to Detect Heart Failure With Preserved Ejection Fraction (hfpef) Using Computer Aided Auscultation of Phonocardiogram
Authors: Damani Devanshi N , Damani Shivam , Kapoor Anoushka , Kulkarni Kanchan , Shivaram Suganti , Araoz Philip A , Reddy Yogesh , Borlaug Barry A , Poigai Arunachalam Shivaram
Published: June 2023

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is an increasingly common clinical syndrome with diagnostic challenges and no effective treatment. The high heterogeneity of HFpEF clinical syndrome demands novel technologies to distinguish from heart failure with reduced ejection Fraction (HFrEF). Currently, invasive hemodynamic exercise testing is performed to evaluate for HFpEF with right heart catheterization.

Hypothesis:
We hypothesize that a deep learning model can noninvasively detect patients with HFpEF using phonocardiogram (PCG).

Methods:
Eligible patients undergoing right heart catheterization were recruited after IRB approval. Eko duo stethoscope was used to record simultaneous ECG & PCG at the mitral area on the patients prior to right heart catheterization at baseline. Each recording was 30 seconds in length with a frequency range between 250 - 5000 Hz. R-wave peak detection was performed & beat to beat PCG annotations were performed. The annotated PCG signals were converted into Mel-frequency cepstral coefficients (MFCC) and padded to account for the difference in lengths. Deep Learning model was developed using a Sequential Neural Network with 80% data to train and validate the model and 20% hold out data was used for testing accuracy of the model. Receiver operating curve (ROC) was obtained to estimate area under the curve (AUC) for performance analysis.

Results:
42 patients were enrolled with 25 patients diagnosed as HFpEF by right heart catheterization and 17 were reported as controls. 2544 & 1771 individual PCG annotations for HFpEF and controls were used for model training/validation and testing. The model performed reasonably well with accuracy of 0.89, F1 score of 0.88, precision of 0.80 and recall of 0.97 on the test data. ROC was obtained with AUC of 0.94.

Conclusions:
The results demonstrate the ability of the deep learning model to noninvasively detect HFpEF using PCG. Larger study is needed to validate these findings.
Abstract 14839: Clinical, Polysomnographic and Echocardiographic Correlates of Excessive Daytime Sleepiness
Authors: Saeed Gul Jana , Aneni Ehimen , Otite Fadar O , Thorn Stephanie , Miller Edward J , Sinusas Albert J , Yaggi Henry K
Published: June 2023

Introduction:
Excessive Daytime Sleepiness (EDS) has been associated with adverse CVD outcomes. However, the mechanisms of elevated CVD risk in persons with EDS remains uncertain. In this study, we examined polysomnographic and echocardiographic correlates of EDS in a population of adults who underwent both sleep and cardiac stress tests.

Methods:
We analyzed data from 264 participants who had an in-lab polysomnogram (PSG) and a cardiac stress test between 2016 and 2019. All patients completed the Epworth Sleepiness Scale (ESS) questionnaire. EDS was categorized into 3 groups no EDS (ESS<10), non-severe EDS (ESS 10-14), and severe EDS (ESS ≥15). T90%, the percentage of sleep time spent with oxygen desaturation < 90%, was categorized into severe (≥ 20%) and non-severe nocturnal hypoxemia (<20%). We assessed the relationship between EDS and CV risk factors, and EDS and echocardiographic parameters of diastolic dysfunction such as the E/e’, E/A ratio, left atrial volume index, tricuspid regurgitation jet velocity, and systolic function (ejection fraction, EF).

Results:
The mean age (SD) of the participants was 59 (11) years, and 59% were female. In logistic regression analysis severe EDS was associated with >3-fold odds of a history of stroke or TIA [a OR 3.2 (95%CI:1.2-8.2), P=0.017] and nearly 4 times the odds of severe nocturnal hypoxemia [aOR 3.8 (95%CI: 1.7-8.6, P=0.002] compared to those with no EDS. We found no other association between EDS and demographic or CV characteristics or PSG variables. In the subset of patients with available echocardiogram data (n=199 - 213), there was no association between EDS and EF or echocardiographic parameters of diastolic dysfunction.

Conclusions:
EDS is strongly associated with severe nocturnal hypoxia and a history of stroke or TIA in adults with OSA. Further studies are needed to characterize the relationship between EDS and CVD.
Abstract 14852: Association Between Features of Adverse Myocardial Function Beyond Ejection Fraction and Outcomes in Heart Failure With Preserved Ejection Fraction
Authors: Peters Anthony , Clare Robert M , Chiswell Karen , Felker Michael , Kelsey Anita M , Mentz Robert J , Devore Adam D
Published: June 2023

Background:
Heart failure (HF) guidelines recommend assessment of left ventricular ejection fraction (LVEF) to classify patients and guide therapy implementation. However, LVEF alone may be insufficient to adequately characterize patients with HF with mildly reduced or preserved LVEF. Recommendations on additional testing are lacking, and echocardiographic features beyond LVEF are relatively under-investigated in the real-world HFpEF population despite their ubiquity in clinical practice.

Methods:
Using an echocardiographic and clinical database from a large US healthcare system, patients with HFpEF were defined as those with LVEF>40% and at least one distinct billing diagnosis of acute or chronic HF. The association of the following metrics with mortality was evaluated: global longitudinal strain (GLS>-16), left atrial volume (LAVi>28), left ventricular hypertrophy (LVH), and E/e’>13 & e’<9. A multivariable model for mortality was constructed including age, sex, and key co-morbidities followed by stepwise selection of echocardiographic features.

Results:
Among 2,337 patients with complete echocardiographic data, the following features were associated with all-cause mortality over 3 years of follow-up: E/e’ + e’, GLS, LAVi (all p<0.01). In the multivariable model (c-index=0.65), only GLS was independently associated with all-cause mortality (HR 1.35 [1.11-1.63], p=0.002). In the setting of normal LVEF (>55%), 498 patients (39.7%) demonstrated decreased GLS. This cohort demonstrated higher event rates compared to patients with normal GLS irrespective of LVEF (
Figure, Panel A-B
).

Conclusions:
In a large, real-world HFpEF population, echocardiographic features of HFpEF, led by GLS, are associated with adverse outcomes irrespective of LVEF. A large subset of patients demonstrate adverse myocardial function by GLS despite preserved LVEF and may represent a key cohort of interest for therapy implementation and future clinical studies.
Abstract 14857: Usefulness of Invasive Hemodynamics in the Evaluation of Patients With Paradoxical Low Gradient Severe Aortic Stenosis
Authors: Jain Pranav , Nieves Ricardo A , Shpilsky Daniel L , Katz William , Suffoletto Matthew S , Soman Prem
Published: June 2023

Background:
Management of patients with paradoxical (ejection fraction > 50%) low gradient (< 40 mm Hg mean) severe (valve area < 1 cm
2
) aortic stenosis (PLAS) on ECHO is controversial. We studied the role of invasive hemodynamics (CATH) in evaluating these patients.

Methods:
In this single center retrospective cohort study, patients who underwent CATH for evaluation of PLAS on ECHO were divided into a “concordant” group (CG) when CATH aortic valve area (AVA) was < 1.0 cm
2
and a “discordant” group (DG) when CATH AVA was > 1.0 cm
2
. ECHO features, aortic valve replacement (AVR), and all-cause mortality were compared between the two groups. T-test, Chi-square test, and Kaplan-Meier analysis were performed. P-value of < 0.05 was considered statistically significant.

Results:
Among 76 PLAS patients who underwent CATH, the AVA was discordant in 21/76 (27.6%). DG patients were younger (72.2 vs. 78.7 y, p = 0.008). Other demographics including the Charlson comorbidity index (CCI) were similar. Dimensionless index (DI) was lower in CG than in DG (0.24 ±0.042 vs. 0.274 ± 0.041, p = 0.002) and % with DI < 0.25 was higher in CG (55.6% vs. 28.7%, p = 0.03). Other ECHO parameters including mean gradient, left ventricular outflow tract (LVOT) diameter, Vmax LVOT, AVA
i
, stroke volume index, and flow rate (AVA x mean velocity) were not different. More patients underwent AVR in CG (49/55, 89%) compared to DG (12/21, 57%, p = 0.001). Overall survival based on all-cause mortality was similar after AVR in both groups (p = 0.695, median follow up 1105.5 days). In DG, survival was better with AVR than with medical therapy alone (p = 0.049). CCI was not different in patients with AVR versus those without (p = 0.102).

Conclusion:
¼ of patients with PLAS on ECHO had discordant AVA on CATH. DI < 0.25 occurred more frequently in the CG cohort. Even in the DG, survival was better with AVR.

Clinical Implication:
AVR confers a survival advantage in patients with PLAS on ECHO, and should be considered regardless of AVA on CATH.
Abstract 14892: Interaction of β
IV
-Spectrin/STAT3 is Responsible for Orienting Concentric versus Eccentric Cardiomyocyte Hypertrophy
Authors: Nassal Drew , Mohta Shivangi , Patel Nehal , xu Xianyao , Han Mei , Mohler Peter J , Hund Thomas J
Published: June 2023

Cardiac hypertrophy is critical in the development of heart failure following chronic cardiac stress. In pressure overload, hypertrophy is divided by early adaptive remodeling defined by concentric growth, while chronic hypertrophy associates with eccentric growth and loss in cardiac output. The mechanisms regulating this transition and the impact each profile has in influencing heart function are largely unknown. Previous work identified a role for the structural protein βIV-spectrin and its interaction with the transcription factor, STAT3, in coordinating hypertrophic profiles. Specifically, mice expressing truncated βIV-spectrin lacking interaction with the hypertrophic signaling molecule CaMKII (qv
3J
mice) were resistant to βIV-spectrin degradation and maintained concentric hypertrophy and ejection fraction (EF) compared to WT following 6 weeks transaortic constriction (TAC). Alternatively, mutant βIV-spectrin mice (qv
4J
) lacking the STAT3/βIV-spectrin binding domain lead to cytosolic redistribution of STAT3 and associated with reduced EF and LV dilation consistent in eccentric remodeling, suggesting STAT3/βIV-spectrin is a key regulator of hypertrophic profiles and function. This relationship was further examined by adenoviral overexpression of the hypertrophic driver, MEK1/2, on isolated myocytes. As expected, MEK increased the width of WT myocytes, while qv
4J
myocytes increased in length. However, application of STAT3 inhibitor S3I-201 on qv
4J
myocytes reoriented these cells to growth in width. Additionally, in vivo application of S3I-201 to qv
4J
mice was able to restore LV wall thickness and EF over 2 weeks, reinforcing STAT3 as a determinant of hypertrophic profiles. Evaluation of cardiac gene expression profiles from these backgrounds identified consistent elevations in microtubule subunits associated with eccentric growth patterns. Indeed, microtubule growth assays revealed qv
4J
myocytes to express significantly enhanced microtubule stability which could be reversed through S3I-201 STAT3 inhibition. Together, these data identify a novel role for βIV-spectrin/STAT3 and microtubule stability in tuning specific hypertrophic profiles and cardiac function.
Abstract 14905: A Combination of Polygenic Risk Scores for Coronary Artery Disease and for Circulating Blood Lipids Predicts the Incidence of Myocardial Infarction and Coronary Revascularization
Authors: Manikpurage Hasanga D , Li Zhonglin , Eslami Aida , Bosse Yohan , Mathieu Patrick , Arsenault Benoit J , Theriault Sebastien
Published: June 2023

Introduction:
Estimating the genetic risk of developing complex diseases, such as coronary artery disease (CAD), is now possible by aggregating data from genome-wide association studies (GWAS) into polygenic risk scores (PRS). This study aims to evaluate the performance of PRS derived from CAD (PRS
CAD
) and blood lipids GWAS to predict severe CAD defined as myocardial infarction or coronary revascularization (MI-REVASC).

Methods:
Using nuclear magnetic resonance data from UK Biobank (UKB, n=90300), we conducted 29 GWAS for blood lipids (9 for fatty acids and 20 for lipoproteins). Summary statistics of these GWAS were then used to derive PRS in the rest of UKB (n=318422, median follow-up = 12.6 years). A PRS
CAD
was also calculated using the publicly available GWAS from the CARDIoGRAMplusC4D consortium. All PRS included >1.1 million of genetic variants and were calculated using LDpred2. Hazard Ratio (HR) for incident MI-REVASC (n=10935) are reported with their 95% CIs, for 1-SD increase of each PRS. Selected independent PRS were combined into multivariate Cox regression models, for which predictive performance was evaluated. All models were adjusted for age, sex and genetic principal components.

Results:
Out of 30 PRS, 28 were significantly associated with incident MI-REVASC; PRS
CAD
showed the strongest association (HR=1.60 [1.57-1.63], p<10e-300), whereas PRS for small LDL particles (sLDL-P) was the most associated blood lipids PRS (HR=1.14 [1.12-1.16], p=7.63e-42). The optimal model included PRS for CAD, sLDL-P, HDL-C and the PUFA/MUFA (poly-/mono- unsaturated fatty acids) ratio. Discriminative capacities for incident MI-REVASC were significantly increased in the model including PRS
CAD
(C-statistic (C) = 0.744 [0.739-0.748]) compared to the model without PRS (C= 0.710 [0.705-0.714]). No significant difference was observed when independent blood lipids PRS were added to the model (C= 0.745 [0.741 to 0.749]).

Conclusions:
Although independently associated with the incidence of severe CAD, blood lipids PRS provide little improvement in the predictive performance when added to PRS
CAD
.