bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13308: Complementary Investigations of Plasma Proteomics Identify Novel Protein Associations With Incident Diabetes and Glucose Metabolism
Authors: Mi Michael Y , Cronje Helene T , Austin Thomas R , Biggs Mary L , Siscovick David S , Lemaitre Rozenn N , Psaty Bruce M , Tracy Russell P , Djousse Luc , Kizer Jorge R , IX Joachim H , Sotoodehnia Nona , Rao Prashant , Robbins Jeremy M , Barber Jacob L , Sarzynski Mark A , Clish Clary , Bouchard Claude , Mukamal Ken J , Jensen Majken K , Gerszten Robert E
Published: June 2023

Introduction:
Type 2 diabetes (T2D) is a cardiovascular disease risk equivalent and likely results from broad metabolic changes, which high throughput proteomics have helped to unravel. Prior studies are limited by proteomic coverage, cross sectional design, and lack of physiologic phenotyping.

Hypothesis:
Complementary proteomic studies of incident T2D and physiologic responses to an intravenous glucose tolerance test (IVGTT) will identify novel proteins with roles in glucose homeostasis and future risk of T2D.

Methods:
Cardiovascular Health Study (CHS) and HERITAGE study participants without diabetes underwent SomaScan
®
profiling of 4,776 plasma proteins. HERITAGE participants underwent IVGTT, from which insulin sensitivity index (S
I
), acute insulin response to glucose (AIR
G
), and glucose effectiveness (S
G
) were derived. We used Cox regression to test protein associations with 18-year incident T2D in CHS, and multivariable linear regression to test protein associations with IVGTT measures in HERITAGE.

Results:
In CHS (N = 2631, 74 ± 5 years, 62% female, 14% Black), 57 proteins were significantly associated with incident T2D after comprehensive covariate and multiple testing adjustment. Of these, 44, 9, and 8 were associated with S
I
, AIR
G
, and S
G
respectively in HERITAGE (N = 752, 35 ± 14 years, 55% female, 38% Black) (Figure). Notable findings include beta-glucuronidase, which associated with increased T2D risk (HR 1.46 per SD increase in log
2
protein level) and lower S
G
, suggesting a role in insulin-independent glucose disposal, and thrombospondin-2, which associated with increased T2D risk (HR 1.26 per SD), lower AIR
G
, and not with S
I
, indicating that it may be a marker of pancreatic dysfunction.

Conclusions:
By integrating proteomics from two complementary prospective cohorts using different but related outcomes, we identified 34 novel protein-T2D associations, and characterized their relationship with physiologic axes of glucose metabolism.
Abstract 13342: Validation of the European Society of Cardiology Systematic Coronary Risk Evaluation 2 Prediction Algorithms in a Non-European (United States) Contemporary, Community-Based Historical Cohort
Authors: Medina-Inojosa Betsy J , Medina-Inojosa Jose R , Sheffeh Mohammad Ali , Bianchettin Rosana , Lerman Amir , Lopez-Jimenez Francisco
Published: June 2023

Introduction:
Newly developed Systematic Coronary Risk Evaluation-2 (SCORE-2) and the version for older people [(SCORE2-OP) ≥70 years] algorithms for 10-yr incident cardiovascular disease (CVD) have been derived incorporating European and US populations. Its performance has not been externally validated in community-based populations representative of real-world clinical practice.

Hypothesis:
We tested the hypothesis that the SCORE-2 and SCORE2-OP algorithms will accurately estimate 10-yr risk of first-onset CVD in this population.

Methods:
Consecutive patients who, between 1998-2000, sought primary care in Olmsted county, MN, and were followed-up using the Rochester Epidemiology Project. Inclusion criteria were set as those used in the derivation of the original algorithm. The composite outcome of CVD was defined as first myocardial infarction, ischemic stroke, or cardiovascular mortality. We compared predicted and observed events and generated C-statistics across predefined risk subgroups.

Results:
We included 22,858 adults, mean age of 55.11±11.58 (13.50% >70 yr) 54% females. After a mean follow-up of 9.55±1.5 yr, 2,145 events were observed. 6.39% of subjects for SCORE-2 and 59.88% using SCORE2-OP were considered at high risk. Overall, the SCORE-2 had better discrimination than the SCORE2-OP (C-statistic: 0.72 and 0.64, respectively) (Fig B-D). The algorithms performed better in individuals 50-69 yr while underpredicting in younger individuals and overpredicting CVD in ages above 70 (in the low and moderate risk group) (Fig A-C). Prediction was mostly similar between men, women and middle-aged individuals but demonstrated pronounced underprediction in older men (Fig B-D).

Conclusions:
The SCORE-2 Risk prediction tool performed with marginal results whereas the SCORE2-OP had poor performance when predicting CVD events in a community cohort representing real-world clinical practice in a non-European population.
Abstract 13346: Long Term, Synergistic Benefit of Transmyocardial Laser Revascularization and Platelet Rich Plasma - Significant Improvement of Global Longitudinal Strain in Coronary Artery Bypass Graft Patients
Authors: Khalpey Zain , Aslam Usman , Deckwa Jessa
Published: June 2023

Introduction:
Transmyocardial revascularization (TMR) is a procedure designed to treat patients with end-stage coronary artery disease (CAD). TMR creates myocardial micropores which undergo endothelialization and redistribute ischemic stress, thereby improving regional wall motion. Autologous platelet rich plasma (PRP) growth factors contribute to endothelialization and neovascularization. In this study, we evaluate the effectiveness of TMR combined with PRP to improve cardiac function in patients undergoing CABG using echocardiograms.

Methods:
A single-center, single surgeon retrospective analysis of CABG patients was performed (2019-2021). Patients in the TMR group had ten channels (7 Watts/channel) created in the infero-lateral wall of the left ventricle (LV) and those in the PRP group had autologous PRP extract injected(1ml, without calcium) in the same area. In patients treated with both TMR and PRP, ten channels were made in the inferolateral LV with PRP extract injected in the peri-TMR zone, 5mm adjacent to the channels. Post-operative ejection fraction (EF) and global longitudinal strain (GLS) were measured using speckle tracking up to one year.

Results:
Fifty-two patients (71% men, mean age 66y ±9.04y) were enrolled in the study and randomized to four experimental groups: CABG only (n=16); CABG/TMR (n=17); CABG/PRP (n=10); and CABG/TMR/PRP (n=9). At one-year follow-up, patients treated with both TMR and PRP had a significant improvement in average GLS (-15.96, p= 0.02) compared to TMR alone (-13.78, p= 0.26) and PRP alone (-15.79, p= 0.08). Patients treated with TMR and PRP also had a significant rise in post-operative EF (57.78%, SD +/- 6.18) compared to TMR alone (55.0%, SD +/- 6.85) and PRP alone (49.5%, SD +/- 11.65).

Conclusions:
TMR with PRP extract treatment at the time of CABG confers a significant one year improvement in cardiac function as measured by LVEF and GLS. These outcome metrics highlight cardiac remodeling and can mitigate the incidence of heart failure readmissions. With further prospective trials and longer follow-up periods, concomitant adjunctive TMR with PRP extract therapy at time of CABG may have durable and significant cardiac scar remodeling benefits leading to heart recovery in CABG patients.
Abstract 13358: A Platform for the Personalized Management of Diabetes and Cardiovascular Disease at Population Scale With Data From Multiple Sensors
Authors: Senanayake Ransalu , Ferstad Johannes O , Thapa Isha , Giammarino Flavia , Vasu Megana , Zaharieva Dessi , Prahalad Priya , Maahs David M , Rosenthal David N , Rodriguez Fatima , Bambos Nicholas , Miller Daniel , Shin Andrew , Roth Stephen J , Guestrin Carlos , Fox Emily B , Scheinker David
Published: June 2023

Introduction:
The American Heart Association has identified the design of mobile health (mHealth) tools to improve the management of diabetes and cardiovascular disease and to prevent unplanned hospital readmissions as a priority.

Methods:
We developed HEART, an open source platform for personalized telehealth at population scale based on data from internet-connected health sensors and data extracted from the electronic medical record (EMR). Health sensors include scales, blood pressure monitors, activity monitors, continuous glucose monitors, and insulin pumps. EMR data include gender, age, race, reason for admission, all surgical procedures performed, and all medications prescribed upon discharge. We collected admission and readmission data for all cardiology patients at an academic pediatric medical center over the last 7 years.

Results:
HEART has five independent modules (Figure): 1) a data processing module that pulls data in from a variety of devices and EHR feeds, 2) an algorithm module that identifies reasons why a provider may want to contact a patient and ranks patients for contact, 3) a visual interface module that summarizes population data and provides additional details for patients selected by the provider, 4) an intervention module that facilitates messages being sent to providers and documented in the EMR, and 5) a user tracking module that monitors providers use. HEART ranks the entire population cared for by a clinic and allows providers to identify easily those patients who may benefit most from a secure message, telemedicine contact, or in-person visit. There were 5,011 admissions to cardiology among 2,916 patients, with 1000 urgent readmissions for 512 patients and 35,300 outpatient clinic visits.

Conclusions:
HEART is a population-level framework to facilitate personalized mHealth with data from a variety of sensors and EMR data feeds. It may facilitate outpatient monitoring as part of an effort to prevent unplanned hospital readmission.
Abstract 13367: APOE ε4 Carriage Associates With Improved Myocardial Performance in Older Age
Authors: Topriceanu Constantin-Cristian , Webber Matthew , Chan Fiona , Moon James , Chaturvedi Nishi , Hughes Alun , Schott Jonathan , Richards Marcus , Captur Gabriella
Published: June 2023

Introduction:
Although
APOE ε
4 allele carriage confers a risk of coronary disease, its persistence in human populations might be explained by certain survival advantages (antagonistic pleiotropy)
.

Hypothesis:
Combining data from two British cohorts– the 1946 National Survey of Health and Development (NSHD) and Southall and Brent Revised (SABRE)–we explored whether
APOE ε
4 carriage associates with beneficial or unfavorable left ventricular (LV) structural and functional echocardiography parameters in older age.

Methods:
Based on the presence of
APOE
ε
4, genotypes were divided into:
APOE
ε
4 (ε2ε4, ε3ε4,
ε
4
ε
4) and non-
APOE
ε
4 carriers. Echocardiographic data included: LV ejection fraction, E/e’, systolic and diastolic posterior wall and interventricular septal thickness (LVPWT
s/d
, IVS
s/d
), LV mass and the ratio of the LV stroke volume to the LV myocardial volume called myocardial contraction fraction (MCF). Generalized linear models explored associations between
APOE ε
4 genotypes as exposures and echocardiographic biomarkers as outcomes. As APOE genotype is a genetic instrumental variable (unconfounded), Model 1 was unadjusted. Model 2 was adjusted for factors associated with the outcome (sex and socio-economic position) to yield more precise estimates; subsequent models were individually adjusted for mediators (body mass index, cardiovascular disease [CVD], high cholesterol and hypertension) to explore mechanistic pathways. Random-effects meta-analyses were performed across the cohorts.

Results:
2596 participants were included. Compared to non-
APOE
ε
4 carriers,
APOE
ε
4 carriers had similar cardiac phenotypes in terms of EF, E/e’, LVPWT
s/d
, IVS
s/d
and LV mass but had a 4% higher MCF (95% confidence interval [CI]: 1–7%,
p
=0.016) which persisted in Model 2 (95% CI 1–7%,
p
=0.008) but was attenuated to 3% after adjustment for CVD, diabetes and hypertension (all 95% CI 0–6% all
p
<0.070).

Conclusions:
APOE
ε
4 carriage associates with improved myocardial performance in older age resulting in greater LV stroke volume generation per 1 mL of myocardium. This potentially favorable cardiac phenotype adds to the growing number of reported survival advantages attributed to
APOE
ε4 carriage that might collectively explain its persistence in humans.
Abstract 13374: Effect of Moderate to Strenuous Exercise on Biological Aging as Determined by Artificial-Enabled Electrocardiography
Authors: Rajai Nazanin , Medina-Inojosa Betsy , Sheffeh Mohammad Ali , Baez Suarez Abraham , Nyman Mark A , Attia Zachi , Lerman Lilach O , Medina-Inojosa Jose R , Lopez-Jimenez Francisco , Lerman Amir
Published: June 2023

Introduction:
The physiological changes associated with aging have deleterious effects on cardiovascular function. In addition, increasing evidence showed the effect of exercise on improving cardiovascular health and reducing the aging process. The present study sought to demonstrate the association between exercise and biological age, estimated by our previously reported method using artificial intelligence-enabled electrocardiography (ECG).

Methods:
This retrospective observational study enrolled adults aged ≥18 years who have been evaluated at Mayo Clinic between 2019-2022 and completed the exercise questionnaire. The total time spent in moderate to strenuous exercise was calculated by multiplying the number of days engaging in exercise per week by the average minutes per day. The biological age was determined by applying our previously developed convolutional neural network model on the 12-lead ECG records (AI-ECG). The ECG records were within one year of subjects’ visits (in case of multiple visits, the closest one to the questionnaire was chosen). Positive Age-Gap (AI-ECG minus chronological age) reflects a person identified as being older by AI-ECG compared to his/her chronological age.

Results:
A total of 268,002 subjects (51% female) were recruited (mean age 59.7±16.4 years). Of those, 25.7% were not engaged in any exercise. The median day of engaging in exercise was 3 (Interquartile range, 2,5) per week, and the average time of exercising was 31.3±30 minutes/day. Age-Gap diminished progressively with increased duration of moderate to strenuous exercise (Figure 1). Linear regression analysis revealed exercise is an independent predictor of Age-Gap, (β= -0.043, 95%CI, -0.045 and -0.041, p<0.001).

Conclusions:
Engaging in moderate to strenuous exercise is associated with slower biological aging relative to chronological age as determined by AI-enabled ECG.
Abstract 13376: Sleep-Disordered Breathing is Associated With Larger Ventricular Repolarization Instability
Authors: Solhjoo Soroosh , Haigney Mark C , Siddharthan Trishul , Koch Abigail L , Crainiceanu Ciprian M , Punjabi Naresh M
Published: June 2023

Introduction:
Sleep-disordered breathing (SDB) is a common disorder in the general population that is associated with adverse cardiovascular events, such as sudden cardiac death, but the underlying mechanisms are unclear.

Hypothesis:
Ventricular repolarization instability is greater in those with severe SDB than those without SDB, independent of other risk factors.

Methods:
Among the participants of the Sleep Heart Health Study (SHHS), we identified those with SDB who had no diagnosed cardiovascular disease or other factors that could affect cardiac repolarization. Severe SDB was defined as having a respiratory disturbance index (RDI) > 33 events/hour (top 95%ile of the SHHS cohort). We also identified a group of participants matched to the severe SDB group on age, sex, BMI, and race and had RDI < 1.33 events/hour (bottom 25%ile; without SDB). Each group consisted of 61 (45 M and 16 F) participants. Oxygen saturation levels (SpO
2
) were used to measure hypoxemia burden as the percentage of sleep time with SpO
2
< 90% (T90). Heart rate (HR), heart rate variability (SDNN), and QT variability index (QTVI, a measure of ventricular repolarization instability) were calculated from one-lead ECG recordings. Student’s
t-
test was used to assess statistical associations.

Results:
The SDB group had a larger T90 than those without SDB (11.39 ± 1.42% vs 1.32 ± 0.61%, P < 0.001). Participants with SDB also had greater mean HR (P = 0.028), SDNN (P = 0.017), and QTVI (P = 0.027) than those without SDB. Based on a multivariable linear model that included hypoxemia burden, age, BMI, and smoking status, T90 was the only independent predictor of QTVI (P = 0.022).

Conclusion:
SDB is associated with higher HR, HRV, and QTVI, an indicator of increased instability in ventricular repolarization leading to increased risk for cardiac arrhythmias and sudden cardiac death. The severity of the destabilizing effect of SDB on ventricular repolarization appears to be modified by hypoxemia burden.
Abstract 13387: Perceived Quality of Care Differs Across Demographic Groups and is Associated With Incident Heart Failure and Total Mortality: The Atherosclerosis Risk in Communities (Aric) Study
Authors: jefferson artrish , Ndumele Chiadi E , Mathews Lena M , Palta Priya , Shah Amil M , Zhang Sui , Matsushita Kunihiro , Cooper Lisa , Windham Beverly , Tcheugui Justin , Coresh Joe
Published: June 2023

Background:
Disparities in the patient care experience are an important aspect of social determinants of health. However, the clinical impact of patient perceptions of their care experience is not well understood, especially among persons at risk for heart failure (HF)

Methods:
We studied 5,052 Visit 5 ARIC participants (mean age 76, 23% Black, 58% women) without clinical HF, who were classified as having stage A (HF risk factors) or stage B (subclinical cardiac dysfunction by echocardiogram or cardiac biomarkers) HF. We examined responses to the ARIC Access and Quality of Care (QOC) Questionnaire data, which included the following 4 questions: “Did providers (1) listen carefully; (2) explain procedures and tests clearly; (3) show respect and (4) spend enough time during visits? Using chi squared tests, we compared responses across sociodemographic groups (race, sex and the socioeconomic status [SES] variables of education, income, and area deprivation index [each categorized]). We used Cox regression models to assess associations of responses with a composite of incident HF and total mortality after adjusting for sociodemographics and CVD risk factors.

Results:
Individuals of Black race or with lower SES were more likely to answer “never” or “sometimes” (vs “always” or “usually”) to each of the 4 questions (all p<0.001). Over a median follow-up of 6.4 years (1,249 events), answering “never” to providers listening carefully, showing respect, or spending enough time were each associated with greater risk of HF/mortality (Table). Answering “never” to 3 to 4 of the questions was associated with a HR of 2.74 (95% CI: 1.41-5.33) for HF/mortality compared to answering “always” on all of the questions.

Conclusions:
Among persons at risk for HF, those of Black race or with low SES were more likely to perceive lower quality of care, which was in turn linked to increased risk for HF or mortality. Enhancing patient-provider relationships may improve health equity in those at high HF risk.
Abstract 13429: A Systematic Review and Meta-Analysis of Comparative Studies of Postoperative Atrial Fibrillation in Obstructive Sleep Apnea Patients Undergoing Coronary Artery Bypass Grafting
Authors: Mondal Avilash , Katukuri Nishanth , Pingili Adhvithi , Sanku Koushik , TAJDIN BORZOO , Zahdeh Tamer , Cherukuri Akhila S , JALILI HAMIDREZA , Bahadoran Pooriya , Srikanth Sashwath , Desai Rupak
Published: June 2023

Background:
Post-CABG Atrial Fibrillation (PCAF) is linked to higher mortality, morbidity, and healthcare costs. Obstructive Sleep Apnea (OSA) has been studied as a risk factor for PCAF in a few studies. In this study, we sought to review and analyze the association between OSA and PCAF.

Methods:
We systematically searched PubMed, Scopus, and EMBASE for studies on OSA as predictors of PCAF using relevant keywords through June 2022. Random effects models were used to estimate pooled rates of PCAF with subgroup analysis. I
2
statistics were used to report inter-study heterogeneity. Leave-one-out meta-analysis was performed to evaluate the effect of each study on the overall estimate.

Results:
A total of 15 (N= 534387) studies were included between 2008-2021 in our Systematic review/Meta-analysis (Median follow-up duration: 29 days; mean age: 59-72 years; Males: 68.4%). 8 US-based studies, with the rest from Europe and South Asia, were included. A total of 34654 PCAF events were recorded. Pooled analysis of unadjusted (OR 1.23, 95%CI 1.07-1.42, p<0.01) and adjusted (1.24, 95%CI 1.10- 1.40, p<0.01) odds of PCAF was higher in OSA vs non-OSA cohorts. Subgroup analysis indicated greater risks of PCAF in prospective studies (OR 1.83, 95% CI 1.24-2.71 p 0.01) but not in retrospective studies. Rates of PCAF were higher in studies reported from other countries compared to the US (1.24 vs 1.18, p<0.001) and with longer follow-up (>3 years) compared to those with shorter follow-up (1 month) duration.

Conclusions:
In this meta-analysis, OSA predicted a nearly 25% higher risk of developing PCAF. Prospective studies assessing the long-term impact of OSA on cardiovascular risk after CABG are warranted to curtail worse outcomes.
Abstract 13430: Arterial Health After Preeclampsia: Role of Chronic Hypertension
Authors: Paquin Amelie , Werlang Ana , Coutinho Thais
Published: June 2023

Introduction:
Preeclampsia (PE) is associated with an increased cardiovascular (CV) risk. Recent data have shown worse left ventricular remodeling and diastolic function in women with PE and persistent hypertension (HTN). To improve our understanding of CV risk after PE, we evaluated the contribution of persistent HTN on arterial health.

Methods:
We recruited 40 women with PE history and 40 age-matched women with normotensive pregnancies (6 months - 6 years post-partum). We comprehensively evaluated measures of arterial health and hemodynamics with validated technique combining applanation tonometry and transthoracic echocardiography. We compared 3 groups: previous PE with persistent HTN (PE-HTN), previous PE with normalized blood pressure (PE-noHTN) and controls. Associations of PE-HTN with arterial health measures were assessed with multivariable linear regression adjusted for age, BSA, heart rate, diabetes, smoking history, serum creatinine and parity.

Results:
Eight (20%) of the post-PE women had persistent HTN. Mean age was 35.8 ± 3.9 years, number of pregnancies was 2.4 ± 1.4, and time since last pregnancy was 2.6 ± 1.2 years, and not different across the 3 groups (P<0.05 for each). Results of the multivariable linear regression models are summarized in the Figure, demonstrating that women with PE-HTN had significantly higher aortic stiffness, wave reflections, pulsatile and steady arterial load than controls. Among women with previous PE whose blood pressure normalized postpartum, arterial stiffness, wave reflections and steady arterial load were also worse compared to controls, albeit with smaller effect size (p<0.05).

Conclusions:
This is the first study to demonstrate the contribution of persistent HTN on worse arterial health following PE. Since measures of arterial health are associated with CV events in the population, women with PE-HTN may represent a higher risk subgroup who could benefit from targeted primary prevention strategies.
Abstract 13431: Comparative Evaluation of Diastolic Left Heart Dynamics Post-Mitral Valve Interventions
Authors: Govindarajan Vijay , Kolanjiyil Arun , Johnson Nils , Kee Patrick , Laing Susan T , Kim Hyunggun , Chandran Krishnan B , McPherson David D
Published: June 2023

Introduction:
Mitral valve (MV) leaflet morphology plays an important role insuring efficient, unidirectional blood flow from the left atrium (LA) to ventricle (LV). When treating severe mitral regurgitation (MR), surgical repair, valve replacement, or transcatheter edge-to-edge (E-2-E) repair all provide valid options depending on anatomy and clinical circumstances. These interventions alter the MV morphology, impacting LV filling dynamics. We used fluid-structure interactions (FSI) to evaluate LV filling dynamics after MV interventions, taking into consideration full left-heart (LH) dynamics.

Methods:
3-D MV model of a patient suffering from severe MR was reconstructed from echocardiographic data. A LH wall motion algorithm was developed and applied to CT-derived LA and LV walls to realistically represent LH dynamics. LH wall motion, MV dynamics and blood flow in LA and LV during MV function was simulated using a strongly coupled fluid structure interaction approach. Virtual interventions using a surgical 33mm bioprosthetic valve (BPV) and transcatheter E-2-E repair were performed and evaluated.

Results:
Our FSI model predicted a physiological vortex ring developing in the LV for the pre-op MV during early diastole. BPV produced complex asymmetrical vortices. Due to its double orifice, the E-2-E clip produced two separate vortex rings with the largest velocity magnitude. Of all the three treatments, BPV had the greatest leaflet deformation rate.

Conclusion:
This model provides realistic quantitative insights into post-op filling dynamics that can be used to personalize and optimize valve intervention. These methodologies may help clinicians to realistically predict and evaluate patient-specific LV filling dynamics to tailor MV interventions.
Abstract 13440: Effect of Pemvidutide (ALT-801), a Novel GLP-1/Glucagon Dual Receptor Agonist, on Pathogenic Lipid Mediators
Authors: Plutzky Jorge , Harris M. Scott S , Alonso Cristina , Suschak John , Noor Mustafa , Ortiz Pablo , Georges Bertrand , Rader Daniel J , Roberts Scot S , Browne Sarah K
Published: June 2023

Introduction:
GLP-1 based agents are receiving intense attention for their potential to decrease CV risk. Pemvidutide is a unique, balanced GLP-1/glucagon dual receptor agonist (RA) combining the anorectic effects of GLP-1 RA with the increased energy expenditure and lipid-lowering effects of glucagon RA. In a 12-week double-blind clinical trial in subjects with overweight/obesity, pemvidutide reduced body weight by 10.3% and significantly decreased total cholesterol (-28%), LDL-C (-26%), and triglycerides (-38%). Here we leveraged lipidomics to investigate the effects of pemvidutide on other lipid mediators implicated in atherosclerosis and metabolic syndrome (MetS).

Methods:
Plasma lipidomic mass spectrometry was performed on baseline and Day 84 samples from 34 subjects receiving 1.2 mg, 1.8 mg, or 2.4 mg pemvidutide, or placebo, subcutaneously weekly.

Results:
Pemvidutide achieved significant dose-dependent reductions from baseline across multiple bioactive lipid classes (Figure), including pro-atherogenic lysophosphatidylcholines (Lyso-PC, a major oxidized LDL component), and lipotoxic sphingolipids, including sphingomyelins and ceramides, across the 12 weeks of treatment. Significant decreases were also observed in ether-linked alkyl phosphatidylcholine (PC) and phosphatidyl-ethanolamine (PE) glycerophospholipids, and in shorter chain, more saturated glycerolipids associated with insulin resistance were also observed.

Conclusions:
Pemvidutide induced pronounced, rapid weight loss with substantial decreases in lipotoxic and pro-atherogenic lipid species. These findings support pemvidutide’s potential benefit on obesity-associated CV co-morbidities, including atherosclerosis and MetS.
Abstract 13443: Clinical Outcomes Following Primary Prevention Implantable Cardioverter Defibrillator (ICD) Implantation Among Older Patients With Hypertrophic Cardiomyopathy (HCM)
Authors: Goldstein Sarah A , kennedy kevin , Friedman Daniel , Al-Khatib Sana M , Wang Andrew
Published: June 2023

Introduction:
The clinical benefit of primary prevention ICDs among older patients (age
>
65) with HCM is unclear. This analysis examined procedural complications and post-discharge outcomes among older patients with HCM following initial placement of a primary prevention ICD.
Methods:
The NCDR ICD Registry was queried to identify patients with HCM who received a primary prevention ICD between 2010-2016. Procedure-related adverse event rates were examined. Direct identifiers were used to link patients
>
65 years to CMS claims data. Cox proportional hazard models were used to assess clinical factors associated with post-discharge mortality and hospitalization for cardiac arrest/ventricular arrhythmia (VA). Kaplan Meier curves were generated to depict 5-year outcomes.
Results:
Of 5571 patients with HCM who were included, 1511 (27.1%) were
>
65 years old. Compared with patients < 65 years of age, older patients with HCM were more likely to experience a procedure-related event (2.3% vs 1.5%, p=0.038) and procedure-related death (0.3% vs 0.1%, p=0.024). The variables most strongly associated with post-discharge mortality were older age (aHR 1.8, 95% CI 1.47-2.21), NYHA class (III/IV vs I/II aHR 2.17, 95% CI 1.57-2.98), and LVEF (LVEF
<
35% vs >50% aHR 2.34, 95% CI 1.58-3.48; LVEF 36-50% vs >50% aHR 2.98, 95% CI 2.02-4.4). For the endpoint of hospitalization for cardiac arrest/VA, history of NSVT at the time of device implantation (aHR 2.38, 95% CI 1.62-3.51) and NYHA class (NYHA class III/IV vs I/II aHR 1.84, 95% CI 1.22-2.78) were the strongest predictors. The event-free survival rates are shown (
Figure).
Conclusions:
Procedure-related complication and mortality rates were low, but they occurred more frequently among older patients. Further prospective investigation should focus on whether clinical factors, such as NYHA class and history of NSVT, may be useful in identifying older patients with HCM who are most likely to benefit from a primary prevention ICD.
Abstract 13444: Acute Anemia With Mechanical Circulatory Support; Unmasking the Culprit
Authors: Babayale Omofolarin , Chand Swati , Abbas Syed Faiz , Fashanu Oluwaseun E , Biswas Suman , Parikh Vishal
Published: June 2023

Introduction:
Mechanical circulatory support (MCS) is known to potentiate hemolytic anemia. Nevertheless, patients are also at an increased risk of spontaneous bleeding due to anticoagulation or post-procedural complication. We present two cases of acute anemia due to spontaneous retroperitoneal bleeding following insertion of the Impella assist device.

Case Presentation:
Two male patients aged 65 and 74 presented with cardiogenic shock secondary to ischemic cardiomyopathy with a low ejection fraction of 10% and 15%). Both patients initially had an intra-aortic balloon pump (IABP) inserted. Because of progressively deteriorating hemodynamics, IABP was switched to the Impella 5.5 device through the axillary artery. Following insertion of the Impella, they developed anemia requiring multiple blood transfusions. Despite repositioning of Impella, hemoglobin continued to drop prompting further workup. CT abdomen/pelvis revealed left retroperitoneal hematoma. CT angiogram showed active bleeding from the left L3 lumbar artery in one patient and multiple foci of active arterial extravasation in the other patient. Coil embolization was performed, achieving hemostasis and stabilization of hemoglobin levels in both patients.

Discussion:
Hemolytic anemia associated with the use of the Impella that improves with repositioning or device removal is well known and documented. However, patients with MCS are also at increased risk of spontaneous bleeding due to procedural injury and the use of anticoagulation. We report 2 cases with retroperitoneal bleeding from the lumbar artery diagnosed a few days after the placement of Impella. The occurrence of retroperitoneal hemorrhage was possibly spontaneous due to anticoagulation along with Impella-induced hemolysis resulting in acute anemia. Neither patient had any vascular access through the left groin making post-procedural complications less likely. The concealed nature and non-specific symptoms of retroperitoneal bleed can lead to a delay in diagnosis. Early identification and control of bleeding can prevent fatal outcomes.

Conclusion:
Our cases highlight the importance of clinicians having a broad differential and low threshold to investigate other causes of anemia in patients with MCS.
Abstract 13445: The Prognostic Value of Pulmonary Hypertension and Atrial Fibrillation in Rheumatic Mitral Stenosis
Authors: Choi Jah Yeon Y , Lee Jieun , Choi You-Jung , Choi Byoung Geol , Park Soohyung , Kang Dong Oh , Park Eun Jin , Kim Ji Bak , Roh Seung-young , Choi Cheol Ung , Kim Jin w , KIM Eung Ju , Rha Seung-Woon , Park Chang Gyu , Yong Hwan Seok , Baek Man-Jong , Na Jin O
Published: June 2023

Introduction and Hypothesis:
Rheumatic mitral stenosis (MS) is decreasing in developed countries; however, there has been a substantial number of patients with rheumatic MS in developing countries. Although the current international guideline of valvular heart disease defined the severe MS as MVA below 1.5 cm
2
and the new onset of atrial fibrillation (Afib) and pulmonary hypertension is one of the indications of MV intervention in asymptomatic severe rheumatic MS, there have been scarce supporting data. Therefore, we sought to investigate the prognostic value of Afib and pulmonary hypertension in severe rheumatic MS.

Methods:
We retrospectively collected data on rheumatic MS in a single center from 2006 to 2022. The clinical, echocardiographic characteristics and clinical outcomes were investigated. The incidence of major cardiovascular adverse events (MACE) including all-cause mortality, hospitalization for heart failure, and the thromboembolic event was investigated following 10 years.

Results:
A total of 792 patients were collected. The mean age of the population was 63 years old, the number of females was 71.8%, and the incidence of severe MS (MVA≤1.5 cm
2
) was 37.4%. In patients with severe stenosis, there was no significant difference in MACE in Afib and non-Afib patients during the 10 years follow-up (Figure A). However, the presence of pulmonary hypertension, esp. pulmonary arterial systolic pressure above 50mmHg, demonstrated significantly worse clinical outcomes (Figure B). In multivariable Cox analysis, pulmonary hypertension (PASP≥50mmHg) was a significant prognostic factor of MACE after adjusting other covariables (HR 1.897, 95% CI: 1.352-2.663, p-value <0.001).

Conclusions:
In severe rheumatic MS, the presence of pulmonary hypertension, not Afib, was a significant prognostic factor for clinical outcome. Further study with a larger population would be needed for more precise risk stratification and indication for MV intervention.
Abstract 13453: Caffeine and Development of Gestational Diabetes Mellitus and Preeclampsia: The Boston Birth Cohort
Authors: Kwon Tae Eun , Liu Tiange , Wang Xiaobin , Hong Xiumei , Mueller Noel T
Published: June 2023

Introduction:
Gestational diabetes mellitus (GDM) and preeclampsia (PE) are common pregnancy complications. Some studies have linked self-reported caffeinated coffee and tea intake to lower risks of GDM and PE. But little is known about the associations of objectively measured caffeine exposure during pregnancy with GDM and PE.

Methods:
We used data from pregnant women without pre-existing diabetes or hypertension in the Boston Birth Cohort (enrolled 1998-2016). From cord blood and maternal blood, collected within 72 hours after delivery, we measured caffeine metabolites (caffeine, 1,7-dimethyluric acid, and 3-methylxanthine). We also estimated caffeinated coffee and tea intake in each trimester from a food frequency questionnaire. We examined odds ratios of GDM and PE using logistic regression models after adjusting for confounders. We modeled metabolites in tertiles and continuously and beverage intakes in categories: 0; 1-6 cups/week; ≥7 cups/week.

Results:
In cord blood analyses (n=744; 8% with GDM; 7% with PE), each 1-SD increments in cord caffeine, 1,7-dimethyluric acid, and 3-methylxanthine were associated with 0.71 (95% CI: 0.53, 0.94), 0.80 (95% CI: 0.59, 1.08) and 0.61 (95% CI: 0.43, 0.86) times the odds of GDM, respectively. In maternal blood analyses (n=1097; 8% with GDM; 8% with PE), each 1-SD increments in maternal caffeine and 1,7-dimethyluric acid were associated with 0.81 (95% CI: 0.64, 1.02) and 0.87 (95% CI: 0.68, 1.11) times the odds of GDM, respectively. Caffeine metabolites in cord or maternal blood were not statistically associated with PE. Self-reported coffee intake of ≥7 cups/week was significantly associated with lower odds of GDM (in all trimesters) and lower odds of PE (in 3
rd
trimester) than no coffee intake; whereas tea intake had no significant associations with GDM and PE.

Conclusion:
Our findings suggested that caffeine exposure in pregnancy may be protective against the development of GDM and have little to no association with PE.
Abstract 13458: Sudden Cardiac Arrest in Dialysis Patients: A Community-Based Study
Authors: Uy-Evanado Audrey , Reinier Kyndaron , Chugh Harpriya , Sorenson Chad , Jui Jonathan , Chugh Sumeet S
Published: June 2023

Introduction:
Individuals with end-stage renal disease (ESRD) on hemodialysis (HD) may be at increased risk of sudden cardiac arrest (SCA) during dialysis. However, existing studies are small and there is a lack of population-based data.

Hypothesis:
Patients on dialysis are overrepresented among SCAs occurring in the general population.

Methods:
From the prospective Oregon Sudden Unexpected Death Study, all cases of SCA were ascertained (2002-2017). For each individual, detailed medical history was obtained from hospital records and first responder reports, also capturing patients with history of dialysis. Cases who suffered SCA during dialysis sessions or within an hour after completing dialysis (on-dialysis group) were compared to cases who had SCA at other times (off-dialyses group). We used chi-square and
t-
tests to compare the two groups.

Results:
A total of 4880 SCA cases with clinical data available were ascertained, of which 1023 (21%) had chronic kidney disease (CKD) and 235 were on dialysis (4.8% of all SCA; 23% of patients with CKD). Of the dialysis subgroup, 90 (94%) were on HD, and 6 (6%) on peritoneal dialysis. The on-dialysis group (n=49, 21%) was comprised of 37 (16%) with SCA during HD, and 12 (5%) within 1 hr post-HD. By chance alone, based on estimated weekly time on dialysis, only 6% of SCA events would be expected to be during dialysis (p<0.001). The off-dialysis group (n=184) comprised the majority (79%) of SCA with history of dialysis. There were no significant differences in age, sex and race or BMI between the 2 groups.

Conclusions:
The prevalence of dialysis among total SCA cases was 24-fold higher than the general population on dialysis (0.2%), and risk was elevated >3-fold during HD. These findings suggest potential opportunities for SCA prevention that could be explored in HD techniques as well as awareness and compliance with dialysis.
Abstract 13482: Feasibility Analysis of a Nurse-Led Empowerment-Based Care Model in Supporting Treatment Decision-Making and Self-Care Among Patients With Atrial Fibrillation
Authors: Li Polly W , yu Doris S
Published: June 2023

Introduction:
Patients with atrial fibrillation (AF) play a passive role in the treatment decision-making process, rendering suboptimal medication optimization and poor self-care. This pilot study aimed to examine the feasibility and preliminary effects of a nurse-led empowerment-based intervention among AF patients.

Methods:
This study comprised a pilot randomized controlled trial and an exploratory qualitative phase. AF patients who had moderate to high risk of stroke but not receiving oral anticoagulation were recruited. Participants (N = 40) were randomized in 1:1 ratio to receive the intervention or standard care. The 13-week intervention adopted a novel behavioral activation approach to equip AF patients as an active agent to manage the disease. It consisted of care components to prepare patients for shared decision-making by using a decision aid, an empowerment-based educational module covering relevant AF self-care topics and continuous support through telephone calls. Ten participants in the intervention group attended a qualitative interview to explore their engagement experience and perceived feasibility.

Results:
The intervention was highly feasible and participants gave excellent rating for the satisfaction survey. The overall attendance rate was 82.5%. Compared with the standard care group, the intervention group showed greater improvements in health-related quality of life (HRQoL) [β = -10.617, (95% CI = -20.350 - -0.885), p = 0.033] and AF knowledge [β = 1.950, (95% CI =1.026 - 2.874), p <0.001] at immediate post-intervention. The effects on both outcomes sustained at 6-month follow-up time point. No significant between-group changes in medication adherence, anxiety and depression were detected. Participants in the intervention group were activated to raise their concerns about AF and its treatment with the attending doctors. The qualitative data highlighted the uniqueness of the empowerment process of the intervention in improving their knowledge and self-care behaviors.

Conclusions:
The empowerment-based nurse-led intervention is highly feasible and acceptable for AF patients. It improved HRQoL, AF knowledge and treatment decision making in AF patients. It did not increase anxiety and depression.
Abstract 13531: Hydrogen Sulfide Donor, SG1002, Protects Against Hypertension-Induced Exacerbation of Doxorubicin Cardiotoxicity in Female Mice
Authors: Mauro Adolfo G , Kraskauskas Donatas , Noyelle Emma , Eldessouky Malk , Melendez Giselle C , Lesnefsky Edward , Toldo Stefano , Hundley William G , Salloum Fadi N
Published: June 2023

Background:
Dose-dependent declines in left ventricular ejection fraction (LVEF) and increases in heart failure (HF) limit the administration of doxorubicin [DOX] in the treatment of breast cancer, lymphoma, and leukemia. Cancer patients with hypertension (HTN) experience higher rates of developing HF after DOX and perhaps share mechanistic contributors (e.g., oxidative stress and inflammation) to LVEF declines. Hydrogen sulfide (H
2
S) has been shown to stimulate mitochondrial stability and reduce the residual inflammatory risk in the setting of myocardial infarction.

Hypothesis:
The orally active, slow-releasing H
2
S donor SG1002 attenuates DOX-induced LVEF decline and cardiotoxicity in mice with HTN.

Methods:
Adult female C57BL mice were randomized to either control diet or SG1002-enriched chow to achieve a dosage of 40 mg/kg/day for the duration of the study. Mice underwent osmotic minipump implantation to deliver angiotensin II (ATII) (1500ng·kg
-1
·min
-1
; N=7/group) for 28 days to cause HTN. Seven days following ATII infusion initiation, DOX was delivered i.p., 4 doses of 5 mg/kg every 3 days (cumulative dose: 20mg/kg). Mice underwent tail-cuff blood pressure measurement and echocardiography at baseline, 12 days (post 2
nd
DOX dose) and 28 days post initiation of ATII infusion (Fig A).

Results:
Twenty-eight-day measures in LVEF were lower in HTN animals receiving DOX relative to those without HTN. SG1002-fed mice demonstrated preserved LVEF following DOX (Fig B). Additionally, SG1002-fed mice exhibited an attenuated hypertensive phenotype following ATII infusion (Fig C).

Conclusion:
Our results in female mice indicate that HTN worsens DOX-induced cardiomyopathy, which is attenuated with SG1002 treatment. Interestingly, SG1002 also prevented HTN following ATII infusion in female mice. Further studies are warranted to determine the efficacy of the H
2
S donor, SG1002 to prevent DOX-associated LVEF declines in mice with and without HTN.
Abstract 13537: The Difference Between Cystatin C- and Creatinine-Based Kidney Function Assessment is Associated With Clinical Outcomes, Quality of Life and Frailty in Patients With Heart Failure and Reduced Ejection Fraction: Insights From PARADIGM-HF
Authors: Pinsino Alberto , Carey Matthew R , Syed Husain A , Jennings Douglas L , Mohan Sumit , Takeda Koji , Naka Yoshifumi , Sayer Gabriel T , Uriel Nir , Demmer Ryan T , Colombo Paolo C , Yuzefpolskaya Melana
Published: June 2023

Introduction:
Discrepancies between cystatin C (CysC)- and serum creatinine (sCr)- estimated glomerular filtration rate (eGFR) may reflect sarcopenia and malnutrition. Among pts with heart failure and reduced ejection fraction (HFrEF) enrolled in PARADIGM-HF (Angiotensin Receptor-Neprilysin Inhibitor with Angiotensin-Converting-Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in HF), we investigated the difference between eGFRCysC and eGFRsCr and its association with clinical outcomes, quality of life (QoL) and frailty.

Methods:
Intra-individual differences between eGFRCysC and eGFRsCr (eGFRdiff) were calculated at randomization (n=1,970) and 8-month follow-up (n=1,631). Study outcomes included a composite of cardiovascular (CV) mortality or HF admission, and, separately, CV and all-cause mortality, worsening kidney function, poor QoL and frailty. Worsening HF was defined as outpatient intensification of HF therapy, emergency department visit or HF admission between randomization and 8-month follow-up.

Results:
At randomization, eGFRdiff was >10 and <-10 ml/min/1.73 m
2
in 25 and 36% of the pts, respectively. More negative values of eGFRdiff were associated with worse outcomes (adjusted hazard ratio per 1-standard deviation [SD]: CV mortality or HF admission 1.20, p=.003; CV mortality 1.37, p<.001; all-cause mortality 1.42, p<.001; worsening kidney function 1.30, p=.066). For each 1-SD decrease in eGFRdiff, the prevalence of poor QoL and frailty increased by 28% and 19%, respectively (p ≤.003). Pts with worsening HF had more marked decline in eGFRCysC than eGFRsCr. As a result, worsening HF was associated with a change in 8-month eGFRdiff by -4.7 ml/min/1.73 m
2
(
Figure
).

Conclusions:
In HFrEF pts, discrepancies between eGFRCysC and eGFRsCr are common and are associated with clinical outcomes, QoL and frailty. In pts with worsening HF, sCr may underestimate decline in kidney function due to changes in muscle mass and diet.