bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9588: Intraplaque Myeloperoxidase Activity is a Hallmark of Vulnerable Atherosclerosis and Correlates With Clinical Outcomes
Authors: Nadel James , Tumanov Sergey , Kong Stephanie , Chen Weiyu , Sivasubramaniam Vanathi , Gianotti Nicola , Rashid Imran , Ugander Martin , Jabbour Andrew , Stocker Roland
Published: June 2023

Introduction:
There remains limited means by which to detect unstable atherosclerosis in patients at risk of myocardial infarction and stroke. Myeloperoxidase (MPO) is increased in unstable plaque and causally linked to plaque destabilization and rupture in pre-clinical models. We sought to assess whether MPO activity is greater in vulnerable human carotid and coronary atheroma, and how this relates to adverse cardiovascular events and non-invasive imaging parameters.

Methods:
Carotid endarterectomy specimens (CEA) were collected from 31 patients. Coronary trees were collected from 12 patients undergoing heart transplantation for ischemic cardiomyopathy. MPO activity was assessed through the conversion of hydroethidine added to tissue sections to the MPO-specific adduct 2-chloroethidium (2-Cl-E
+
) and quantified by mass spectrometry. MPO activity was then compared with histologic determination of plaque phenotype and clinical outcomes. MPO activity was additionally assessed in high and low attenuation plaques derived by computed tomography, as well as perivascular adipose tissue (PVAT).

Results:
Unstable CEA had higher MPO activity when compared with stable CEA plaques (n = 26, 4.2 ± 3.1 vs. 0.2 ± 0.3 μmol/mgp; p < 0.0001). Similar results were seen in coronary segments with unstable compared to stable plaque (n = 17, 0.6 ± 0.5 vs. 0.0 ± 0.0 μmol/mgp; p = 0.0006). When comparing MPO activity in CEA to clinical outcomes, asymptomatic and stroke-free patients had lower MPO activity compared to those with symptoms or ipsilateral stroke on neuroimaging (n = 12, 3.7 ± 2.1 vs. 0.1 ± 0.2 μmol/mgp; p

= 0.002). CT-determined plaque attenuation did not identify plaque MPO activity (n = 30, 0.1 ± 0.1 vs. 0.2 ± 0.3 μmol/mgp; p = 0.23) and enzymatically active MPO was not found in PVAT.

Conclusion:
MPO is active within unstable human carotid and coronary plaques and correlates with symptomatic carotid disease and stroke. In addition, current non-invasive imaging parameters do not selectively identify plaques enriched with active MPO. As intraplaque MPO appears to be a hallmark of unstable atherosclerosis and can potentially be imaged non-invasively, further investigation into its potential utility as a diagnostic tool for high-risk atherosclerosis is warranted.
Abstract 9596: An Investigation of Differences in Ideal Cardiovascular Health Between Sexual Minority and Heterosexual Adults: Findings From the National Health and Nutrition Examination Survey (2007-2016)
Authors: Caceres Billy A , Sharma Yashika , Ravindranath Rohith , Ensari Ipek , Streed Carl
Published: June 2023

Introduction:
There is growing evidence that sexual minority (e.g., lesbian, gay, bisexual) adults are at higher risk of cardiovascular disease (CVD) than heterosexual adults. Research on the cardiovascular health (CVH) of sexual minority adults has primarily examined differences in the prevalence of individual CVH metrics rather than comprehensive measures. Therefore, we investigated sexual identity differences in ideal CVH among adults (ages 18-59) in the United States using the American Heart Association’s (AHA) Life’s Simple 7; a composite measure of ideal CVH.

Methods:
We analyzed cross-sectional data from the National Health and Nutrition Examination Survey (2007-2016). Questionnaire, dietary, and physical examination data were used to assess the seven metrics included in the Life's Simple 7 measure. Participants received a score of 0 (poor), 1 (intermediate), or 2 (ideal) for each CVH metric and scores were summed to calculate ideal CVH scores (continuous; range 0-14). We ran sex-stratified regression models adjusted for demographic characteristics and survey year to examine sexual identity differences in ideal CVH scores and ideal CVH (i.e., odds of meeting ideal criteria for ≥5 CVH metrics).

Results:
The sample included 12,832 participants with a mean age of 39.2 (±11.95) of which 5.7% were sexual minority. Compared to heterosexual women, bisexual women had lower ideal CVH scores (
B
= -0.65, 95% CI = -1.02, -0.27) and they were also less likely to meet criteria for ideal CVH (AOR = 0.66, 95% CI = 0.47-0.93). Gay men had higher ideal CVH scores than heterosexual men (
B
= 0.61 95% CI = 0.01, 1.21). Gay (AOR = 2.05, 95% CI = 1.16-3.62) and bisexual (AOR = 2.15, 95% CI = 1.16-3.99) men were more likely than heterosexual men to meet criteria for ideal CVH.

Conclusions:
This is the first representative study to investigate sexual identity differences in ideal CVH. Bisexual women were at higher risk of CVD than heterosexual women, which was attributed to higher odds of current tobacco use and obesity. Gay and bisexual men were at lower risk of CVD than heterosexual men. Future longitudinal research is needed to examine factors that might contribute to CVH disparities among bisexual women. Clinical interventions to reduce CVD risk among bisexual women are needed.
Abstract 9599: Impact of Sex on Outcomes After WATCHMAN FLX Implantation
Authors: Nair Devi , Piccini Jonathan P , Hsu Jonathan C , gibson douglas , Freeman James V , Yeh Robert W , Price Matthew J , Christen Thomas , Allocco Dominic , Kapadia Samir R
Published: June 2023

Introduction:
Female sex is an established, non-modifiable risk factor for adverse outcomes in atrial fibrillation (AF) patients. Left atrial appendage occlusion (LAAO) has been shown to be generally safe and effective for stroke prevention in patients with AF. Data on sex-based outcomes with WATCHMAN FLX is lacking.

Methods:
WATCHMAN FLX patients from the National Cardiovascular Data Registry LAAO Registry between August 5th 2020 and March 31st 2021 were analyzed.

Results:
Women at baseline had a higher average CHA
2
DS
2
-VASc score, were more likely to have a history of transient ischemic attack, thromboembolic event, peripheral or carotid artery disease, fall risk, and chronic lung disease than men. Conversely, history of congestive heart failure, left ventricular dysfunction, hypertension, diabetes, vascular disease, abnormal renal function, cardiomyopathy, non-paroxysmal atrial fibrillation, myocardial infarction, prior cardiac interventions, alcohol use, antiplatelet medication use and non-steroidal anti-inflammatory drug use were all reduced in women compared to men. The early safety endpoint was similar between women and men (
Table
). At 45 days, unadjusted rates of major adverse events were higher in women than men mainly due to differences in major bleeding and pericardial effusion (
Table
). The risk of death was lower in women than men at 45 days. Rates of stroke, major vascular complications, systemic thromboembolism, myocardial infarction, and device-related thrombus were not significantly different between sexes. Adjusted outcomes will be available at the time of the presentation.

Conclusions:
In this national unselected cohort, there are significant sex-based differences in baseline characteristics and comorbidity burden. Women experienced more major adverse events after LAAO than men. Additional research to determine the underlying mechanisms of the increased risk in women and strategies for closing the gap between sexes are needed.
Abstract 9602: Higher Anatomical Syntax Score is Associated With Lower Survival After CABG in the REGROUP Trial
Authors: Zenati Marco A , Habertheuer Andreas , Stock Eileen , Arshanskiy Maria , Hattler Brack , Dematt Ellen , Bhatt Deepak , Biswas Kousick
Published: June 2023

Introduction:
The SYNergy between Percutaneous Coronary Intervention with TAXus and Cardiac Surgery (SYNTAX) score quantifies complexity of coronary artery disease (CAD) using angiographic data to objectively guide mode of revascularization. Recent studies evaluating complexity of CAD by the anatomical SYNTAX score (SS1) and impact on clinical outcomes following CABG have been inconclusive.

Hypothesis:
We sought to investigate the prognostic value of SS1 in predicting survival and incidence of major adverse cardiac events (MACE) following CABG in the REGROUP trial (ClinicalTrials.gov number NCT01850082.)

Methods:
This was a pre-planned sub-analysis of the REGROUP trial which randomized patients undergoing isolated CABG to endoscopic versus open vein harvest at 16 U. S. Veterans Affairs Medical Centers between 2014-2017; The median follow-up was 4.7 years (interquartile range 3.84-5.45). SS1 was extracted for all patients and stratified by terciles. Time-to-event survival analysis was performed for MACE defined as death from any cause, nonfatal myocardial infarction, or repeat revascularization over the study follow-up.

Results:
The mean SS1 for this cohort (N=1,145) was 28.5±11.5 (median 27). Mean age was 66.4±6.90 years, 50.2% were diabetics and 99.5% were males reflecting the Veterans population. According to SS1 terciles, low (<23), intermediate (23-32) and high (>32) SS1 groups comprised 383, 393 and 369 patients, respectively. Over study follow-up, SS1 terciles were associated with all-cause death (log-rank, p=0.012), which occurred in 8.6%, 14.2% and 15.2% of patients respectively (p=0.013). However, SS1 was not associated with higher rates of the composite MACE which occurred in 20.4%, 22.6% and 25.5% of patients (p=0.247).

Conclusions:
Over the REGROUP study follow-up, complexity of CAD evaluated by the SS1 is significantly associated with all-cause death, but not MACE.
Abstract 9607: Sex Differences in Cardiovascular Outcomes in Dialysis Patients
Authors: Shah Silvi , Christianson Annette , Meganathan Karthikeyan , Leonard Anthony , Crews Deidra , Rubinstein Jack , Mitsnefes Mark , Schauer Daniel , Thakar Charuhas
Published: June 2023

Background:
Cardiovascular disease is the leading cause of mortality in patients with kidney failure, and their risk of cardiovascular events is 10 to 20 times higher as compared to the general population. Little is known about sex differences in cardiovascular outcomes in dialysis patients which precludes sex-specific therapies.

Methods:
We evaluated 508,822 patients who initiated dialysis between 1/1/2005 and 12/31/2014 using the United States Renal Data System with linked Medicare claims. We determined rates of hospitalizations for cardiovascular events, defined by acute coronary syndrome, heart failure, and stroke. We examined the association of sex with the outcome of cardiovascular events, cardiovascular death, and all-cause death, using adjusted time-to-event models.

Results:
The mean age of patients in the study cohort was 70±12 years, and 44.7% were women. The cardiovascular event rate was 232 PTPY (95% CI, 231-233), with a higher rate in women than in men (248 PTPY; 95% CI, 247-250 vs. 219 PTPY; 95% CI, 217-220). Women had a 13% higher risk of cardiovascular events than did men (HR, 1.13; 95% CI, 1.11-1.14). Women had a 15% higher risk of heart failure (HR, 1.15; 95% CI, 1.13-1.16), a 29% higher risk of stroke (HR, 1.29; 95% CI, 1.26-1.32), and no difference in risk of acute coronary syndrome (HR, 0.99; 95% CI, 0.97-1.01). Women had a lower risk of cardiovascular death (HR, 0.84; 95% CI, 0.83-0.85), and a lower risk of all-cause death, as compared to men (OR, 0.92; 95% CI, 0.91-0.93).

Conclusion:
Among patients undergoing dialysis, women have a higher risk of cardiovascular events of heart failure and stroke than men. Women have a lower adjusted risk of cardiovascular mortality and all-cause mortality. Further studies are needed to better understand the factors associated with sex differences in cardiovascular outcomes in patients with kidney failure.
Abstract 9608: Upregulation of Cardiac Beta3-Adrenergic Receptor-Activated iNOS Uncoupling Promotes Diabetic Cardiomyopathy in Type II Diabetic Mice: Role of Oxidant Stress
Authors: Cheng Heng-Jie , Cao Jing , Sun Xiaoqiang , Zhao David X , Kitzman Dalane W , Cheng Che Ping
Published: June 2023

Background:
Recent evidence highlights oxidative stress as an important mechanism to cardiac dysfunction in type 2 diabetes (T2D) and altered β
3
-adrenergic receptor (AR)-activated nitric oxide synthase (NOS) pathway contributing to this process. However, the NOS isoforms involved are controversial. The mechanism of how β
3
-AR stimulation impacts ROS, SERCA2a, and cardiac function in T2D is unclear. We tested the hypothesis that oxidant stress from upregulation of LV β
3
-AR-activated iNOS uncoupling promotes T2D cardiomyopathy.

Methods:
We compared myocyte β
1
- and β
3
-AR, NOS, peroxynitrite (NT), NADPH and SERCA2a expressions and myocyte functional responses to β- and β
3
-AR stimulation with isoproterenol (ISO,10
-8
M) and BRL-37344 (BRL,10
-8
M), respectively, in the absence and presence of iNOS inhibitor, 1400W (10
-5
M) of female mice over 14 weeks (W): 7 normal and 7 with T2D induced by 14 W high-fat diet (HFD) intake, but after HFD for 4 W receiving streptozotocin (STZ, 40 mg/kg/day, i.p. 5 days).

Results:
Versus normal myocytes, T2D myocytes had significantly increased protein levels of β
3
-AR (0.25 vs 0.14) and iNOS (0.25 vs 0.15) accompanied with increased oxidative stress indicated by significantly-elevated NT formation, NADPH (P67
-phox
, 33% and p22
-phox
, 29%) and decreased GTPCH expression (0.43 vs 0.85) and activity. T2D myocytes had significantly decreased β
1
-AR (0.35 vs 0.49) and SERCA2a (0.19 vs 0.29). These changes were associated with reduced cell contraction (dL/dt
max
, 75.4 vs 133.7 μm/s), relaxation (dR/dt
max
, 59.6 vs 113.8 μ m/s), and [Ca
2+
]
iT
(0.16 vs 0.21) accompanied by diminished β-AR-stimulated positive inotropic response, but enhanced β
3
-AR-induced negative inotropic response. Only in T2D myocytes, pretreatment with 1400W improved basal cell function and augmented ISO-increased dL/dt
max
(64.5%) and [Ca
2+
]
iT
(29.2%), but significantly limited BRL-induced decrease in dL/dt
max
(12.7%) and [Ca
2+
]
iT
(9.8%).

Conclusions:
T2D is associated with contrasting changes on myocyte β
1
- and β
3
-AR expression with decreased SERCA2a and increased iNOS. Upregulation of β
3
-AR triggers iNOS uncoupling, leading to oxidative stress, thus promoting intrinsic myocyte dysfunction with impaired [Ca
2+
]
i
regulation and reduced β-AR reserve.
Abstract 9620: External Validation of Deep Learning-Based Echocardiography Algorithms to Automate View Selection and Annotation of the Echocardiogram
Authors: Teramoto Kanako , Hung Chung-Lieh , Frost Matthew , Svedlund Sara , Saraste Antti , Hage Camilla A , Nelson Lauren , Lagerstrm Fermr Maria , Gan Li-ming , Hummel Yoran M , Chandramouli Chanchal , Ling Lieng , Anand Inder S , Richards Mark , Lund Lars H , Shah Sanjiv J , Lam Carolyn S , Tromp Jasper
Published: June 2023

Background:
Manual measurements of echocardiography are time-consuming, error-prone, and highly user-dependent - all of which can be overcome with deep learning (DL) algorithms.

Methods:
We validated the automated DL measurement of the left ventricle (LV) and left atrial (LA) global longitudinal strain (GLS) and 20 conventional echocardiographic measurements using the Us.ai DL workflow. The workflow uses convolutional neural networks (CNNs) to automatically classify 2D videos and Doppler images with accuracies between 0.91-0.99. Separate CNNs automatically annotate and assess individual videos and images. We validated automated measurement in (1) an internal test set and (2) externally against core-lab measurements in the multinational PROMIS-HFpEF study. We compared the association of automated and manual parameters with N-terminal pro-B-type natriuretic peptide (NT-proBNP) in PROMIS-HFpEF.

Results:
The DL workflow successfully analysed 198 studies with an average of 7.8 minutes per study, with 100% reproducibility in the external validation set. In the internal validation set (N=86), automated LA (r=0.77, mean absolute error [MAE]=8.9%) and LV (r=0.91, MAE=2.8%) GLS showed good agreement with manual measurements. In the external dataset, automated measurements showed good agreement with the manual measurements, with an MAE range of 6.8 mL for LV volumes, 7.1% for LV ejection fraction, and 1.7 for the ratio of the mitral inflow E wave to the tissue Doppler e' wave (
Table
). Automated strain measurements showed good agreement (LV GLS: r=0.74, MAE=2.7%, and LA GLS: r=0.80, MAE=4.8%) with core lab measurements in PROMIS-HFpEF. Lastly, automated and manual measurements were similarly associated with NT-proBNP.

Conclusions:
DL-based algorithms can successfully classify and annotate echocardiographic studies, including LA and LV GLS. DL algorithms might increase reproducibility and democratise the use of strain measurements in clinical practice.
Abstract 9705: Diastolic Blood Pressure and Intensive Blood Pressure Control on Cognitive Outcomes: Insights From the SPRINT Trial
Authors: Li Sitong , Jiang Chao , Wang Yufeng , Lai Yiwei , HE liu , Jiang Chen-Xi , Tang Ribo , Sang Caihua , Long Deyong , Du Xin , Dong jz , Ma Changsheng
Published: June 2023

Introduction:
The potential benefits or harms of intensive systolic blood pressure (SBP) lowering on cognitive function in individuals with low diastolic blood pressure (DBP) remain unclear.

Hypothesis:
The effects of intensive SBP lowering on cognitive outcomes were consistent across baseline DBP levels.

Methods:
In this post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), 8563 participants with at least one follow-up cognitive assessment were included. Cognitive outcomes were the occurrence of probable dementia, mild cognitive impairment (MCI), and a composite of probable dementia or MCI. Cox regression models and likelihood ratio tests were used to assess the interaction between DBP quartiles and intensive SBP control on cognitive outcomes.

Results:
The incidence rates of cognitive outcomes among participants in the lowest DBP quartile were higher than those in the other three DBP quartiles (Figure 1). However, participants in the intensive group had a lower incidence rate of probable dementia or MCI than those in the standard group, regardless of DBP quartiles. There were no significant interactions between SBP intervention and DBP quartiles for probable dementia (
P
for interaction =0.06), MCI (
P
for interaction =0.80), or a composite of probable dementia or MCI (
P
for interaction =0.24) (Figure 2).

Conclusions:
In this post hoc analysis of the SPRINT study, patients with lower DBP had a higher incidence of cognitive impairment. However, the effects of intensive SBP lowering on cognitive outcomes were consistent across different DBP groups.
Abstract 9706: A Novel High Energy Phosphate Source Resuscitates Poorly Functioning Donor Hearts
Authors: Elgebaly Salwa A , Poston Robert , Van Buren Charles , Todd Robert , Arafa Reem , El-Khazragy Nashwa , Rabie Mostafa , Mohamed Ahmed , Ahmed Lamiaa , El Sayed Nesrine
Published: June 2023

Introduction:
Over 60% of the time donor hearts cannot be
utilized
for transplant, mostly because of poor left ventricular ejection fraction (EF) of ≤40% due to stress cardiomyopathy (i.e., demand ischemia) with depletion of myocardial adenosine triphosphate (ATP). The bioenergetic cyclocreatine phosphate (CCrP) is an
FDA Orphan
Designated
Drug
for heart transplantation
. When CCrP is given
prophylactically
in an isoprenaline (ISO) rat model of demand ischemia, it restored ATP and maintained contractility.

Hypothesis:
We hypothesized that administering CCrP
therapeutically
after ISO-induced myocardial dysfunction in rats (simulating rejected donor hearts), will prevent ischemic injury and sustain long-term restoration of EF.

Methods:
Wistar male rats (180-220 g) were injected SC with ISO (85 and 170 mg/kg/day) for two consecutive days. CCrP (n=6, 0.8 gm/kg/day ip) and saline control (n=4) were administered
1 hour
after completing the course of ISO injections and then daily for 2 weeks. A negative control group was injected with saline (n=4). Serum CK-MB and ECG/ST were measured 24 hours after last ISO injection. Evidence of stress cardiomyopathy was assessed after 14 days by ECHO analysis for EF and levels of hs-Troponin I (TnI) and BNP. One-way ANOVA analysis was used.

Results:
Table I shows two main benefits of
therapeutically
administered CCrP in this stress cardiomyopathy model: 1) poor heart function was quickly restored in the
acute phase
(24 hours), as indicated by normal ECG/ST and CK-MB levels; and 2) the restoration of function was sustained over the long term (14 days), as indicated by normal EF% and levels of hs-TnI and BNP.

Conclusions:
The bioenergetic CCrP is a novel cardioprotective drug that appears to
salvage
cardiac dysfunction
and restore
normal EF%
in a rat model of stress cardiomyopathy. If this benefit translates into clinical organ donors with poor heart function, CCrP could be used to increase heart utilization for transplantation.
Abstract 9772: Paroxysmal Atrial Fibrillation Among Pulmonary Embolism Patients; Insight From the 2019 National Inpatient Sample
Authors: Verma Renuka , Kumar Nomesh , Ramphul Kamleshun , Ramphul Yogeshwaree , Sombans Shaheen , Kumari Komal , Lohana Petras , Arti Fnu
Published: June 2023

Introduction:
Various factors can trigger events of Pulmonary Embolism(PE). Several studies have linked cardiac arrhythmias such as Paroxysmal Atrial Fibrillation (PAF) with a higher risk of multiple cardiovascular and pulmonary complications. As there is a paucity of data on the risk factors for an event of PAF among PE patients and the factors contributing to death, we conducted a retrospective analysis using the 2019 National Inpatient Sample(NIS).

Methods:
Our study focused on finding patients with a principal diagnosis of Pulmonary Embolism and a diagnosis of Paroxysmal Atrial Fibrillation. A multivariable regression model evaluated several risk factors for PAF incidence among PE patients and their possible mortality risks.

Results:
A total of 188,850 cases of PE were observed in our study, including 9,960 (5.3%) cases of PAF. Hyperlipidemia (aOR 1.348, 95% CI 1.290-1.409, p<0.01), hypertension (aOR 1.988, 95% CI 1.887-2.095, p<0.01), and old myocardial infarct (aOR 1.574, 95% CI 1.463-1.693, p<0.01) predisposed to PAF among PE, while females (aOR: 0.873, 95% CI 0.837-0.910, p<0.01), patients with obesity (aOR 0.858, 95% CI 0.818-0.900, p<0.01), and those classified as racially Black (aOR 0.603, 95% CI 0.534-0.681, p<0.01), and Hispanic (aOR 0.653, 95% CI 0.562-0.758, p<0.01) (compared to group excluding Whites, Blacks and Hispanics) reduced their risk. An in-hospital mortality rate of 4.0% was also estimated as 395 patients with PAF died. PAF patients with PE had a higher chance of dying if they also had a diagnosis of diabetes (aOR 1.347, 95% CI 1.070-1.695, p=0.011), whereas those who were obese (aOR 0.421, 95% CI 0.311-0.570, p<0.01), with hyperlipidemia (aOR 0.732, 95% CI 0.590-0.909, p<0.01), and smokers (aOR 0.751, 95% CI 0.606-0.931, p<0.01) expressed a lower risk of mortality. PAF patients with PE reported a higher overall risk of death during hospitalization (aOR 1.322, 95% CI 1.190-1.469, p<0.01).

Conclusions:
Patients with a diagnosis of PAF while admitted with PE showed a higher risk of mortality. Several factors influenced the presence of PAF among PE patients. It is thus essential for physicians to monitor various cardiovascular complications and arrhythmias in patients admitted with PE.
Abstract 9783: Relationship Between Abnormal P Wave Axis, Chronic Obstructive Pulmonary Disease And Mortality In The General Population
Authors: Kazibwe Richard , Ahmad Muhammad , Thazhathuveetil Kunahamed Luqman Arafath , Chen Haiying , Yeboah Joseph , Soliman Elsayed Z
Published: June 2023

Background:
Vertical P-wave axis is frequently observed in the electrocardiograms (ECGs) of patients with chronic obstructive pulmonary disease (COPD). However, it is unclear whether its presence modifies the association of COPD with mortality.

Methods:
The analysis included 7,359 participants with ECG data from the Third National Health and Nutrition Examination Survey (NHANES-III) who were free of cardiovascular disease (CVD) at enrollment. Abnormal P-wave axis (aPWA) was defined as values above 75° from digitally recorded and centrally read ECGs. COPD was self-reported as either prior history of emphysema or a current diagnosis of chronic bronchitis. National Death Index was used to identify the date of death and cause of death. Multivariable Cox proportional hazard analysis was used to examine the association of COPD with all-cause mortality among study participants stratified by aPWA.

Results:
About 5.8% (n=422) and 21.8% (n=1,607) of the participants had COPD and aPWA at baseline, respectively. Over a median follow-up of 14 years, 2,435 deaths occurred. Participants with concomitant presence of aPWA and COPD (n=172) experienced higher death rates (73.9 per 1,000 person-years (PY)) compared to those with either COPD or aPWA alone (36.4 per 1,000 PY and 31.1 per 1,000 PY), respectively. In multivariable-adjusted models, there was a significant COPD by aPWA interaction (p=0.04). A stronger association between COPD and mortality was observed in the presence, compared to the absence, of aPWA. Similarly, a stronger association between aPWA and mortality was observed in the presence, compared to the absence, of COPD (
Figure)
.

Conclusions:
Concomitant presence of aPWA and COPD carries a higher risk of mortality. P-wave axis, reported routinely on ECG printout, may identify a subgroup of COPD patients who are at a higher risk of poor outcomes. Further research is needed to examine whether intensive control of risk factors and disease management modify this risk.
Abstract 9800: Racial Differences in Donor-Derived and Mitochondrial Cell-Free Dna Could Explain Inferior Outcomes in Black Heart Transplant Patients, on Behalf of the Graft Investigators
Authors: Shah Palak , Agbor-Enoh Sean , Lee Seiyon , Andargie Temesgen , Sinha Shashank S , Kong Hyesik , Henry Lawrence , Park Woojin , McNair Erick , Tchoukina Inna , Shah Keyur B , Najjar Samer S , Hsu Steven , Rodrigo Maria , Jang Moon K , Marboe Charles , Berry Gerald J , Valantine Hannah A
Published: June 2023

Introduction:
Black heart transplant patients are at higher risk of acute rejection (AR) and death than White patients. Our group has shown that %donor-derived cell-free DNA (%ddcfDNA) is a sensitive and specific marker of AR in heart transplantation. Cell-free mitochondrial DNA (cfmtDNA) has been linked to allograft dysfunction and may mechanistically implicated in inferior outcomes for Black heart transplant recipients.

Hypothesis:
Higher levels of allograft injury when quantitated using %ddcfDNA and total cfmtDNA will be seen in Black heart transplant patients as compared to White patients.

Methods:
The Genomic Research Alliance for Transplantation (GRAfT) is a multicenter, prospective, longitudinal cohort study of heart transplant patients transplanted between 2015 and 2021. We included Black and White patients and shotgun sequencing was used to quantitate %ddcfDNA and polymerase chain reaction (PCR) to quantitate total cfmtDNA levels. AR was defined as grade ≥2R cellular rejection or pAMR ≥1 antibody-mediated rejection (AMR).

Results:
We included 151 patients (73 Blacks and 78 Whites), the median age was 56y (29% Female sex). Patients of both racial groups had comparable baseline characteristics. There were a ~1100 ddcfDNA and cfmtDNA measures included in the analysis. At 18-months, the incidence of AR was 2.8% in White patients and 9.2% in Black patients (p<0.01). The diagnostic accuracy of %ddcfDNA to detect AR was comparable between Black and White patients (0.90 vs. 0.83, p=0.19). The %ddcfDNA and cfmtDNA was higher at serial time points after transplant in Black compared to White patients (Figure). CfmtDNA levels were also elevated with AMR which occurred almost exclusively in Black patients (No rejection: 146,345 copies/ul, AMR: 242,238 copies/ul; p=0.004).

Conclusions:
Elevated levels of %ddcfDNA and cfmtDNA after heart transplant may explain the higher incidence of AR, AMR, and inferior outcomes in Black heart transplant recipients.
Abstract 9831: Antithrombotic Regimens After Transcatheter Aortic Valve Replacement: Comparison of Medium-Term Outcomes
Authors: Naser Jwan A , Gochanour Benjamin R , Scott Christopher , Kennedy Austin M , Luis Sushil A , Greason Kevin , Crestanello Juan A , Gulati Rajiv , Eleid Mackram F , Nkomo Vuyisile T , Pislaru Sorin V
Published: June 2023

Introduction:
Bioprosthetic valve thrombosis is a recognized cause of bioprosthetic valve dysfunction. It was found to be associated with accelerated bioprosthetic degeneration and higher rates of valve re-replacement.

Hypothesis:
Warfarin for 3 months after transcatheter aortic valve replacement (TAVR) protects against accelerated valve degeneration and is therefore associated with better outcomes compared to dual antiplatelet (DAPT) and single antiplatelet therapies (SAPT).

Methods:
Adult patients who underwent TAVR (2012-2019) were identified retrospectively (n=1,501). Patients with atrial fibrillation were excluded (n=657). Patients were classified into warfarin, DAPT, and SAPT groups based on antithrombotic regimen. Structural valve degeneration (SVD) was considered when patients developed new ≥ moderate trans-prosthetic regurgitation, increase in mean gradients ≥10 mmHg from baseline, or when gradients exceeded 20 mmHg. Discharge date was considered time zero.

Results:
Overall, 844 patients [mean age 80 (±9), 43% females, mean Society of Thoracic Surgeons risk score 6.7 (±5.0)] were included. Warfarin was used in 633 (75%) patients, DAPT in 164 (19%), and SAPT in 47 (6%). Median follow-up time was 2.5 (IQR 1.2-3.9) years. There was no difference in outcomes of ischemic stroke, death, valve re-intervention, SVD, their composite endpoint, or hemorrhagic stroke and hemorrhagic stroke/RBC transfusion events (Figures 1 & 2), even after adjustment for confounders.

Conclusion:
Warfarin after TAVR was not associated with better clinical or hemodynamic outcomes or with worse adverse events compared to DAPT and SAPT.
Abstract 9866: A Cardiac Scale Based Digital Intervention Showed Improved Performance versus Usual Care for Detecting Worsening Heart Failure Events
Authors: Yazdi Daniel , Centen Corey , Ozonat Kivanc , Smith Sarah , Obert Kimberly , Kendziorski Sara , Horgan Meg , Sciandra Joann , Murphy Karen , Mehra Vishal C
Published: June 2023

Introduction:
There is a need for non-invasive, remote solutions for detecting worsening heart failure (HF) events. The Bodyport Cardiac Scale is a physical platform with sensors that measure hemodynamic signals through the user’s feet, including electrocardiogram, ballistocardiogram, and impedance plethysmogram. Biomarkers extracted from these signals are used as inputs to the fluid alert algorithm to detect worsening HF events.

Hypothesis:
The Bodyport fluid alert algorithm is able to detect worsening HF events more accurately and earlier compared to traditional weight-based monitoring.

Methods:
In a real-world deployment at Geisinger Health System, 97 patients with a history of HF and enrolled in remote care management were provided with a cardiac scale and monitored for 90 days. The care team had access to weight and was blinded to other biomarkers. Weight-based alerts were generated if a subject gained more than 3 lbs in 1 day or 5 lbs in a week. The fluid alert algorithm incorporates parameters derived from the impedance plethysmogram, weight change, and pulse rate. Alerts were classified as true positive if a worsening HF event requiring IV diuresis occurred within 15 days of the alert.

Results:
Forty-eight participants (49.5%) were female and the average age was 74 years. Daily scale adherence was 86.2%. The cardiac scale detected 12 of 12 (100%) HF events compared to 8 of 12 (67%) using the weight-based rule, p = 0.008. The median time from alert to event increased from 5 to 9 days and the alert burden decreased from 26 to 15 alerts/100 patients/week with the fluid alert algorithm. The area under the receiver operating characteristic curve for the algorithm is 0.85.

Conclusions:
The fluid alert algorithm is able to detect worsening HF events more accurately, earlier, and with a reduced alert burden compared to traditional weight monitoring. The cardiac scale and fluid alert algorithm have the potential to significantly enhance the remote management of HF patients.
Abstract 9881: Effects of CPAP on Very Short-Term Blood Pressure Variability Associated With Sleep-Disordered Breathing Determined by Pulse-Transit-Time-Based Blood Pressure Measurements
Authors: Misaka Tomofumi , Yoshihisa Akiomi , Ohara Himika , Sugawara Yukiko , Tomita Yusuke , Tetsuya Tani , Ichimura Shohei , Sato Yu , Yokokawa Tetsuro , Abe Satoshi , Sato Takamasa , Kaneshiro Takashi , Oikawa Masayoshi , KOBAYASHI ATSUSHI , Takeishi Yasuchika
Published: June 2023

Background:
Sleep-disordered breathing (SDB) and blood pressure (BP) variability are closely associated with cardiovascular diseases. We have recently reported that pulse-transit-time (PTT) has enabled to monitor the beat-to-beat BP, identifying a strong relationship between the severity of SDB and the extent to very short-term BP variability. Here, we investigated the effects of continuous positive airway pressure (CPAP) on very short-term BP variability.

Methods:
We studied 57 patients (mean age 61 years old, male 42) with SDB who underwent the full polysomnography on two consecutive days for diagnosis (baseline) and CPAP. PTT was continuously monitored together, and PTT-based BP values were measured on a beat-to-beat basis. PTT index was defined as the average number of acute transient rises in BP (≥12 mmHg) within 30 seconds per hour.

Results:
Apnea-hypopnea index (AHI) was decreased from 46.5±22.4 to 13.7±15.0 (P<0.01) by CPAP. CPAP significantly lowered the average value of systolic PTT-based BP from 121±21 to 118±20 mmHg (P=0.04). Importantly, CPAP significantly reduced the PTT index from 31.4±20.1 to 20.8±15.6 (P<0.01) as well as the standard deviation (SD) of systolic PTT-BP from 5.3±1.9 to 4.9±1.4 mmHg (P=0.01), suggesting that very short-term BP variability was improved by CPAP (
Figure
). The changes in PTT index after CPAP were significantly correlated with the improvement in AHI (R=0.55), oxygen desaturation index (R=0.36), minimal SpO
2
(R=0.48), mean SpO
2
(R=0.46), and arousal index (R=0.58). In multivariate linear regression analysis, the change in AHI was the independent factor to determine the reduction of the PTT index after CPAP.

Conclusion:
PTT-based BP discovered the improvement in very short-term BP variability associated with SDB events by CPAP therapy.
Abstract 9886: Outcome of Pancreatic Cancer Patients Following Hospitalization for Acute Myocardial Infarction: Perspective From the National Inpatient Sample
Authors: Kumar Nomesh , Verma Renuka , Ramphul Kamleshun , Mejias Stephanie G , Sombans Shaheen , Kumari Komal , Ramphul Yogeshwaree , Arti Fnu , Lohana Petras
Published: June 2023

Introduction:
Pancreatic cancer (PC) has induced a higher risk of a hypercoagulable state that can further lead to various complications such as Acute Myocardial Infarction (AMI). There is a lack of data on the outcomes of PC patients following an episode of AMI.

Method:
A retrospective analysis was performed via the 2019 National Inpatient Sample (NIS). We identified a principal diagnosis of AMI and a diagnosis of PC (ICD-10 'C25.x') at any level. Patient characteristics (sex, race, diabetes, mean age, hypertension, hyperlipidemia, and smoking history) were compared, and the risk of mortality in PC patients was estimated via multivariable regression analysis.

Results:
In total, 555 (0.1%) PC cases were found among all hospitalized cases of AMI in the United States in 2019. We also found that 63.1% were males, 46.8% had diabetes, 85.6% had hypertension, 58.6% had hyperlipidemia, 45.9% reported a smoking history, and 73.0% were Whites. Among the PC patients, 120 (22.4%) patients underwent PCI. Unfortunately, 65 (11.7%) patients with PC died (aOR 2.595, 95% CI 1.995-3.375, p<0.01). Among PC patients with AMI, a lower mortality risk was seen among smokers (aOR: 0.221, 95% CI 0.110-0.444, p<0.01), diabetics (aOR: 0.369, 95% CI 0.193-0.707, p<0.01), and those with hypertension (aOR: 0.114, 95% CI: 0.054-0.239, p<0.01). The mean age of all PC patients was 72.77 years (SEM: 0.421), while non-PC patients were younger (66.92 years, SEM:0.016). PC patients that died were also older, with a mean age of 75.38 (SEM:1.542), compared to non-PC patients that died following AMI (mean age 73.41, SEM 0.071).

Conclusion:
Our analysis found that pancreatic cancer raised the risk of mortality among AMI cases. While most cases of pancreatic cancer tend to have an overall poor prognosis, physicians are encouraged to investigate further other risk factors that can complicate their hospitalizations.
Abstract 9920: Utilizing Synchronous Healthcare Delivery to Optimize the Use of Guideline Directed Medical Therapies in Patients With Type 2 Diabetes: Results From the DECIDE-CV Clinic
Authors: Gedeon Tara , Ghandour Amale , Zhang Guang , Razaguizad Amir , Balram Sharmila , Peters Tricia , Suri Rita , Fantus Ivan G , Giannetti Nadia , Verma Atul , Mavrakanas Thomas , Tsoukas Michael , Sharma Abhinav
Published: June 2023

Introduction:
The high burden of comorbidities among patients with Type 2 Diabetes (T2D) may contribute to the low use of guideline directed medical therapies (GDMT) that improve CV outcomes, including sodium glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like-peptide-1 receptor agonists (GLP1RA).

Hypothesis:
The DECIDE-CV clinic at McGill University (Montreal, Canada) is a novel synchronous healthcare program whereby patients with T2D are seen at each visit simultaneously by a cardiologist, endocrinologist, and nephrologist to enable rapid GDMT implementation. We hypothesized that synchronous healthcare delivery would increase SGLT2i and GLP1RA use among multimorbid patients with T2D.

Methods:
We conducted a pre/post analysis of GDMT use throughout patient follow-up in the DECIDE-CV clinic. We evaluated the first 76 patients (2020-10-26 to 2022-04-18) and used Canadian diabetes/CV guidelines with Quebec medication coverage criteria to assess eligibility for SGLT2i and GLP1RA. A 2-sample test for proportions compared use of GDMT at baseline and follow-up.

Results:
At baseline, the mean age of patients was 68.5 years old, 79% were male, 33% were non-white minorities, 50% had CKD, 64% had HF, and 58% had ASCVD. The median eGFR was 60.1 ml/min/1.73m
2
(IQR 40.7, 93.8), median NT-proBNP was 434 (IQR 123, 1425), and median HbA1c was 7.3% (IQR 6.8, 8.7). At baseline only 37% were prescribed a SGLT2i and 3% a GLP1RA despite being guideline eligible and having medication coverage. After the first visit, the use of therapies significantly increased to 90% for SGLT2i and 39% for GLP1RA. At the end of follow-up, 98% were prescribed a SGLT2i and 57% were prescribed a GLP1RA (P-value comparing proportion GDMT < 0.001; Figure 1).

Conclusions:
Among patients eligible for GDMT, the initial use of SGLT2i and GLP1RA was low. Our model of synchronous healthcare delivery in a multi-comorbid population, significantly increased the use of SGLT2i and GLP1RA.
Abstract 9930: Exercise-Induced ATP7A, A Cu Transporter for SOD3, Restores Endothelial Dysfunction in Type2 Diabetes via Cysteine Oxidation of Protein Kinase G
Authors: Varadarajan Sudhahar , Abdelsaid Kareem , Boatwright Harriet , McMenamin Malgorzata , Eaton Philip , Ushio-Fukai Masuko , Fukai Tohru
Published: June 2023

Background:
Exercise training protects against type2 diabetes (T2D)-induced endothelial dysfunction which is mediated through eNOS uncoupling-induced O
2
-, but its underlying mechanisms are not fully understood. Cu transporter ATP7A is required for full activity of antioxidant Cu enzyme extracellular SOD (SOD3) that scavenges O
2
-
to generate H
2
O
2
that has been proposed to function as a signaling molecule to mediate endothelium-dependent vasorelaxation (EDR) in T2D instead of nitric oxide (NO). However, role of ATP7A and its link with H
2
O
2
signaling in exercise-induced restoration of endothelial function in T2D is entirely unknown.

Results:
Here we show that ATP7A protein (49%), SOD3 activity (51%) and extracellular H
2
O
2
levels as well as EDR in blood vessels of high fat diet-induced T2D mice were significantly decreased compared to those of control C57Bl6 mice, which were restored by volunteer wheel exercise (2 weeks) or in T2D/ATP7A overexpressing mice. Of note, exercise-induced restoration of EDR in T2D mice was inhibited by PEG-catalase infusion or direct application of catalase to vessels, or in ATP7A dysfunctional ATP7A
mut
mice or T2D/SOD3 knockout (KO) mice, but not by eNOS inhibitor, L-NAME. This suggests that exercise-induced ATP7A-SOD3 axis-derived H
2
O
2
, but not eNOS/NO, plays a role in this effect. We then examined downstream targets of exercise-induced H
2
O
2
in blood vessels and found that protein kinase G (PKG)1α that is shown to be activated by exogenous H
2
O
2
via oxidation at Cys42 was sulfenylated (CysOH formed)(2.3-fold increase) in response to exercise in aorta of T2D, but not control, mice. This T2D-specific exercise-induced CysOH formaton of PKG1a in vascular tissue was inhibited by T2D/ ATP7A
mut
mice or T2D/SOD3 KO mice or PEG-catalase treatment. Functionally, “redox-dead” PKG1a Cys42Ser knock-in mutant mice blocked exercise-induced restoration of EDR in T2D, not control mice.

Conclusion:
Exercise-induced ATP7A promotes SOD3-mediated out-side in H
2
O
2
signaling, which contributes to restore EC dysfunction in T2D via PKG1α oxidation at Cys42.
Abstract 9969: Number of Calcified Coronary Arteries and Prediction of Cardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis
Authors: Allen Tara S , Criqui Michael H , Allison Matthew A , Denenberg Julie O , Bhatia Harpreet S
Published: June 2023

Introduction:
Current coronary artery calcium (CAC) scoring methods do not account for the number of vessels affected. We assessed the hypothesis that the number of vessels with CAC would be associated with higher risk for incident cardiovascular disease (CVD) outcomes, even after accounting for traditional risk factors, and that adding this metric to current risk scores would improve event prediction.

Methods:
We analyzed data from 3,255 MESA participants with baseline CAC and event follow-up. Cox proportional hazard regression analyses evaluated the association between number of affected vessels and incident myocardial infarction (MI), hard coronary artery disease (CHD), and hard CVD, adjusting for the ASCVD score and CAC volume and density. Area under the receiver operator curves (AUC) assessed event discrimination by adding number of vessels with CAC to current risk models.

Results:
At baseline [mean age 66 years (SD 9.6); 1,893 female (58%)], 1,086 participants (33%) had CAC in 1 vessel, 832 in 2 (26%), 987 in 3 (30%), and 385 in 4 (12%). Over a median of 15.5 years, 275 developed MI, 408 CHD, and 598 CVD. Multivariable-adjusted risk was higher with CAC in 3-4 vs 1 vessel for all outcomes (Table) and with 3-4 vs 2-vessels for CHD and CVD (HR 1.36, 95% CI 1.0-1.8 and HR 1.30, 95% CI 1.0-1.6). AUC increased after adding the number of vessels with CAC to the ASCVD score for MI (0.5992 to 0.6645, p=0.002), but not for CHD or CVD, and there was no significant increase for any endpoint when added to models already accounting for CAC volume and density.

Conclusions:
In a cohort free of baseline CVD, CAC had similar prevalence in 1, 2, and 3 vessels. After accounting for the ASCVD score and CAC volume and density, CAC in 3-4 vessels still conferred a significantly higher risk for adverse CVD outcomes compared to CAC in 1-2 vessels. Moreover, MI risk prediction was improved with adding the number of vessels with CAC to the ASCVD score, but not when also accounting for CAC volume and density.
Abstract 9991: Index Case of Prosthetic Mitral Valve Dehiscence Secondary to SARS CoV 2 Virus: Histopathologic Evidence of T-cell Mediated Injury
Authors: Ehtesham Moiz , Khan Arshan , Shabbir Muhammad Asim
Published: June 2023

Introduction:
SARS-Cov-2 virus has been shown to inflict damage on native cardiac valvular tissue. We present the index case of prosthetic mitral valve (MV) dehiscence secondary to SARS-Cov-2 virus as evidenced by histopathologic analysis of peri-valvular annular tissue .

Case:
63-year-old male with history of MV replacement 2 years ago presented with complaint of dyspnea for 2 weeks. He was asymptomatic on a cardiology appointment a month ago and had an unremarkable transthoracic echocardiography (TTE) at that time. On arrival, he was hypoxic to 80% on room air and chest exam revealed bibasilar crackles. Complete blood count and electrolytes were within normal ranges. He tested positive for SARS-Cov-2 virus RNA and had a recent family history of COVID-19. Chest X-ray revealed bilateral pulmonary vascular congestion. He was given supplemental oxygen through nasal cannula with improvement in pulse oximetry. Repeat TTE revealed mitral paravalvular leak with suspicion for prosthetic dehiscence. Transesophageal echocardiogram showed multiple jets of severe paravalvular regurgitation and disruption of the MV apparatus. No vegetations were detected on echocardiography. He underwent a pre-operative right heart catheterization which confirmed severe MV regurgitation with pulmonary artery (PA) capillary wedge pressure of 45mmHg (Normal: <12) and a PA pressure of 40mmHg (Normal:<20). Intra-operatively, we found near-complete dehiscence of prosthetic MV with surrounding annular calcifications. Our patient underwent surgical MV replacement with a biosynthetic valve. Histopathologic analysis of the annular tissue revealed myxomatous degeneration and an inflammatory infiltrate of CD4 T helper cells consistent with subacute to chronic inflammation. Of note, neutrophils were not detected which usually signify acute bacterial endocarditis. Tissue and blood cultures remained sterile. Our patient improved hemodynamically after MV replacement and was discharged home in stable condition.

Conclusion:
We propose that SARS-Cov-2 virus may cause prosthetic MV dehiscence through CD4 T cell-mediated damage to annular tissue. Such cases would require surgical valve replacement to manage the resulting hemodynamic compromise.